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1.
Chinese Medical Journal ; (24): 152-161, 2024.
Article in English | WPRIM | ID: wpr-1007681

ABSTRACT

BACKGROUND@#Highly expressed in various human cancers, circular RNA Protein Kinase C Iota (circPRKCI) has been reported to play an important role in cancer development and progression. Herein, we sought to reveal the prognostic and clinical value of circPRKCI expression in diverse human cancers.@*METHODS@#We searched the Pubmed, Web of Science, and the Cochrane Library databases from inception until May 16, 2021. The relationship between circPRKCI expression and cancer patients' survival, including overall survival (OS) and disease-free survival (DFS), was assessed by pooled hazard ratios (HR) with corresponding 95% confidence interval (CI). The correlation between circPRKCI expression and clinical outcomes was evaluated using odds ratios (OR) with corresponding 95% CI. The data were analyzed by STATA software (version 12.0) or Review Manager (RevMan 5.3).@*RESULTS@#A total of 15 studies with 1109 patients were incorporated into our meta-analysis. The results demonstrated that high circPRKCI expression was significantly related to poor OS (HR = 1.96, 95% CI: 1.61, 2.39, P <0.001) when compared with low circPRKCI expression in diverse human cancers. However, elevated circPRKCI expression was not associated with DFS (HR = 1.34, 95% CI: 0.93, 1.95, P = 0.121). Furthermore, the patient with a higher circPRKCI expression was prone to have a larger tumor size, advanced clinical stage, and lymph node metastasis, but it was not significantly correlated with age, gender, and distant metastasis.@*CONCLUSION@#Elevated circPRKCI expression was correlated with worse OS and unfavorable clinical features, suggesting a novel prognostic and predictive role of circPRKCI in diverse human cancers.


Subject(s)
Humans , Prognosis , RNA, Long Noncoding/genetics , Neoplasms/metabolism , Disease-Free Survival , Progression-Free Survival , Lymphatic Metastasis , Biomarkers, Tumor/metabolism
2.
Frontiers of Medicine ; (4): 685-698, 2023.
Article in English | WPRIM | ID: wpr-1010800

ABSTRACT

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.


Subject(s)
Humans , Antineoplastic Agents/therapeutic use , Apoptosis , beta Catenin/metabolism , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Coenzyme A Ligases/metabolism , Leukemia, Myeloid, Acute/metabolism , Lipoylation , Prognosis , Wnt Signaling Pathway
3.
Chinese Journal of Pathology ; (12): 1138-1143, 2023.
Article in Chinese | WPRIM | ID: wpr-1012378

ABSTRACT

Objective: To investigate the clinicopathological features and differential diagnosis of olfactory carcinoma (OC). Methods: Twenty-one cases of sinonasal tumors, including those initially diagnosed as olfactory neuroblastoma (ONB) and those with uncertain diagnosis, were collected from the Department of Pathology, the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2016 to August 2022, among which 3 cases were reclassified as OC. The clinicopathological features were investigated, and the remaining 18 cases were used as control. Results: Of the three OC patients, 2 were male and 1 was female, with an average age of 57 years ranging from 35 to 74 years. Microscopically, the tumor cells were arranged in solid, nested or lobulated patterns with occasional palisading around the solid nests. The stroma was highly vascular with focal neurofibrillary areas. There were prominent rosettes or pseudorosettes formation. The tumor cells were mainly ovoid to spindly with scant to moderate amount of cytoplasm, one or several small nucleoli, and fine chromatin content. Brisk mitotic figures were seen. In all 3 cases of OC, there were scanty atypical glands and some were ciliated. Immunohistochemically, at least one epithelial marker and neuroendocrine marker were diffusely expressed in the tumor. Some of the tumor cells were positive for p40 and p63, and the sustentacular cells showed the expression of S-100 protein. All cases tested were negative for NUT, CD99 and desmin, with intact expression of SMARCA4 (BRG1) and SMARCB1 (INI-1). Ki-67 proliferation index varied from 20% to 80%. Follow-up after 16-18 months showed no mortality with tumor recurrence from 1 patient after 16 months. Conclusion: OC is a rare sinonasal tumor with neuroepithelial differentiation, its histomorphology is diverse, and the combination of immunohistochemical markers is essential for appropriate diagnosis.


Subject(s)
Humans , Male , Female , Middle Aged , Paranasal Sinus Neoplasms/chemistry , Biomarkers, Tumor/metabolism , Carcinoma/chemistry , Diagnosis, Differential , S100 Proteins , DNA Helicases/metabolism , Nuclear Proteins/metabolism , Transcription Factors/metabolism
4.
Chinese Journal of Pathology ; (12): 797-801, 2023.
Article in Chinese | WPRIM | ID: wpr-1012310

ABSTRACT

Objective: To investigate the clinicopathological features, immunophenotype, and genetic alterations of rectal adenocarcinoma with enteroblastic differentiation. Methods: Four cases of rectal adenocarcinoma with enteroblastic differentiation were collected at the Affiliated Hospital of Qingdao University, Qingdao, China (three cases) and Yantai Yeda Hospital of Shandong Province, China (one case) from January to December 2022. Their clinical features were summarized. Hematoxylin and eosin stain and immunohistochemical stain were performed, while next-generation sequencing was performed to reveal the genetic alterations of these cases. Results: All four patients were male with a median age of 65.5 years. The clinical manifestations were changes of stool characteristics, bloody stools and weight loss. All cases showed mixed morphology composed of conventional adenocarcinoma and adenocarcinoma with enteroblastic differentiation. Most of the tumors consisted of glands with tubular and cribriform features. In one case, almost all tumor cells were arranged in papillary structures. The tumor cells with enteroblastic differentiation were columnar, with relatively distinct cell boundaries and characteristic abundant clear cytoplasm, forming fetal gut-like glands. Immunohistochemically, the tumor cells were positive for SALL4 (4/4), Glypican-3 (3/4) and AFP (1/4, focally positive), while p53 stain showed mutated type in 2 cases. The next-generation sequencing revealed that 2 cases had TP53 gene mutation and 1 case had KRAS gene mutation. Conclusions: Rectal adenocarcinoma with enteroblastic differentiation is rare. It shows embryonal differentiation in morphology and immunohistochemistry, and should be distinguished from conventional colorectal adenocarcinoma.


Subject(s)
Humans , Male , Aged , Female , Biomarkers, Tumor/metabolism , Adenocarcinoma/pathology , Colorectal Neoplasms , Rectal Neoplasms/genetics , Cell Differentiation
5.
Chinese Journal of Oncology ; (12): 165-169, 2023.
Article in Chinese | WPRIM | ID: wpr-969820

ABSTRACT

Objective: To observe the clinical pathology features, and immune microenvironment of HER-2 intratumoral heterogeneity breast cancer. Methods: Thirty cases of HER-2 intratumoral heterogeneous breast cancer were retrospectively analyzed in Tianjin Medical University Cancer Institute and Hospital from November 2017 to June 2020. HER-2 expression was detected by immunohistochemistry and verified by dual color silver-enhanced in-situ hybridization (D-SISH). HER-2 intratumoral positive and negative regions were divided. The pathological characteristics, subtype, and the level of tumor infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) were evaluated respectively. Results: The proportion of HER-2 positive cells of the breast cancer ranged from 10% to 90%. The pathological type was mainly invasive non-special typecarcinoma. Six cases presented different pathological types between HER-2 positive and negative regions. The HER-2-positive areas included 2 cases of carcinoma with apocrine differentiation, and the negative areas included 2 cases of invasive micropapillary carcinoma, 1 case of invasive papillary carcinoma, and 1 case of carcinoma with apocrine differentiation. In HER-2 positive regions, 17 cases were Luminal B and 13 cases were HER-2 overexpressed types. There were 22 cases of Luminal B and 8 cases of triple negative tumors in the HER-2 negative areas. The levels of TILs in HER-2 positive and negative areas accounted for 53.3% (16/30) and 26.7% (8/30), respectively, with a statistically significant difference (P=0.035). The positive expression of PD-L1 in HER-2 positive area and HER-2 negative area were 6 cases and 9 cases, respectively. Among 8 cases with HER-2 negative regions containing triple negative components, 4 cases were positive for PD-L1 expression. Conclusions: In the case of HER-2 intratumoral heterogeneity, it is necessary to pay attention to both HER-2 positive and negative regions, and evaluate subtype separately as far as possible. For HER-2 intratumoral heterogeneous breast cancer containing triple negative components, the treatment mode can be optimized by refining the intratumoral expression of PD-L1.


Subject(s)
Humans , Female , Breast Neoplasms/pathology , Retrospective Studies , B7-H1 Antigen/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Carcinoma , Tumor Microenvironment , Triple Negative Breast Neoplasms/pathology , Prognosis , Biomarkers, Tumor/metabolism
6.
Journal of Central South University(Medical Sciences) ; (12): 165-171, 2023.
Article in English | WPRIM | ID: wpr-971382

ABSTRACT

OBJECTIVES@#Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor of head and neck. Screening of target genes for malignant tumor therapy is one of the focuses of cancer research, with proto-oncogene and tumor suppressor gene as the breakthrough. It has become an urgent need to find the target gene related to the treatment and prognosis of LSCC.This study aims to explore the role of Lin28B and C-myc in LSCC by detecting the expressions of these two proteins and analyze the correlation between the expression of Lin28B and C-myc and clinicopathological features and prognosis of LSCC.@*METHODS@#We detected the expression of Lin28B and C-myc proteins in 102 specimens of LSCC and 90 specimens of adjacent tissues by immunochemistry, and analyzed the correlation between Lin28B and C-myc protein expressions in LSCC as well as the correlation between the expressions of the two proteins and the clinicopathological features of LSCC. At the same time, the Kaplan-Meier method was used to analyze the relation between Lin28B and C-myc protein levels with the postoperative survival rate of LSCC patients.@*RESULTS@#The protein levels of Lin28B and C-myc in the LSCC tissnes were significantly higher than those in the adjacent tissues (both P<0.05),and there was a positive correlation between the expression of Lin28B and C-myc in LSCC (r=0.476, P<0.05). The expression of Lin28B protein was closely related to age, lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). while the expression of C-myc protein was closely related to lymph node metastasis, clinical stage, tumor size, and pathological differentiation of LSCC patients (all P<0.05). A relevant survival analysis showed that in patients with higher level of Lin28B (P=0.001) or C-myc protein (P<0.001), the postoperative survival rate was relatively low.@*CONCLUSIONS@#Lin28B and C-myc proteins are highly expressed in LSCC with a positive correlation. Furthermore, they are closely related to lymph node metastasis, clinical stage, tumor size, pathological differentiation and prognosis, suggesting that both Lin28B and C-myc might be involved in the occurrence and development of LSCC.


Subject(s)
Humans , Squamous Cell Carcinoma of Head and Neck , Proto-Oncogene Proteins c-myc/metabolism , Laryngeal Neoplasms/diagnosis , Carcinoma, Squamous Cell/genetics , Lymphatic Metastasis , Prognosis , Head and Neck Neoplasms , Biomarkers, Tumor/metabolism , RNA-Binding Proteins/genetics
7.
Chinese Journal of Oncology ; (12): 330-334, 2023.
Article in Chinese | WPRIM | ID: wpr-984726

ABSTRACT

Objective: To investigate the relationship between miR-199b and clinicopathologic features and prognosis of patients with colorectal cancer. Methods: Cancer tissues and adjacent normal tissues of 202 patients with colorectal cancer treated in Cancer Hospital of Chinese Academy of Medical Sciences from March to December 2011 were collected. Reverse transcription-quantitative real-time polymerase chain reaction was used to detect the expression level of miR-199b in colorectal cancer tissues and corresponding adjacent normal tissues. Kaplan-Meier method and Log rank test were used for survival analysis, and receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of miR-199b in colorectal cancer patients. Results: The relative expression level of miR-199b in colorectal cancer tissues (-7.88±0.11) was lower than that in adjacent normal tissues (-6.49±0.12, P<0.001). The expression level of miR-199b in colorectal cancer tissues with lymph node metastasis (-7.51±0.14) was higher than that in colorectal cancer tissues without lymph node metastasis (-8.23±0.17, P<0.001). The relative expression levels of miR-199b in stage Ⅰ/Ⅱ, Ⅲ and Ⅳ colorectal cancer tissues were gradually increased, which were -8.26±0.17, -7.70±0.16 and -6.57±0.27, respectively, and the difference was statistically significant (P<0.001). The 5-year survival rates of patients with high and low expressions of miR-199b were 75.6% and 84.6%(P=0.045) respectively. ROC curve showed that when miR-199b was -7.965, the area under the curve was 0.578 (95% CI: 0.468, 0.688). Conclusion: The high expression of miR-199b in colorectal cancer tissues is associated with late TNM stage, lymph node metastasis and poor prognosis in colorectal cancer patients, and miR-199b may be used as a potential marker for postoperative progress and prognosis in colorectal cancer patients.


Subject(s)
Humans , MicroRNAs/metabolism , Lymphatic Metastasis , Colorectal Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Prognosis , Gene Expression Regulation, Neoplastic , Kaplan-Meier Estimate
8.
Chinese Journal of Hepatology ; (12): 729-735, 2023.
Article in Chinese | WPRIM | ID: wpr-986202

ABSTRACT

Objective: To investigate the clinicopathological features, treatment, and prognosis of hepatic angiosarcoma. Methods: Clinicopathological data and prognostic conditions of 18 cases with hepatic angiosarcoma were collected retrospectively. The recurrence-free survival rate and overall survival rate were calculated by the Kaplan-Meier method. A Cox regression analysis was used to explore the survival-related risk factors. Results: There were 12 male and 6 female patients, with an average age of 57 (37 ~ 70) years. The tumor's average diameter was 8.40 (2.00 ~ 18.00) cm. Seven cases had multiple tumors, while two cases had large vessel tumor thrombuses. Microscopically, the tumor tissues were irregularly anastomosed, with vascular lacunar or solid bundle-like weaving, and the tissue morphology mimicked capillary hemangioma, cavernous hemangioma, or angioepithelioma, while tumor cells were spindle-shaped or epithelioid, lined with hobnails in the lumen, or formed papillary structures in the lumen. The proportion of highly, moderately, and poorly differentiated tumors was 4:8:6, with six cases having clear tumor boundaries, eight having microvascular tumor thrombi, and sixteen having blood lake formation. Different levels of expression of CD31, CD34, erythroblast transformation-specific related genes, and Fli-1 markers were demonstrated in all of the cases. Four cases had a P53 mutation, and six cases had Ki-67 > 10%. During the follow-up period of 0.23-114.20 months, the five-year recurrence-free survival rate and overall survival rate were 16.7% and 37.2%, respectively. Cox regression multivariate analysis showed that preoperative symptoms and multiple tumors were significant risk factors for recurrence-free survival, while preoperative symptoms and Ki-67 > 10% were significant risk factors for overall survival. Conclusion: Hepatic angiosarcoma is a rare hepatic mesenchymal tumor with high malignancy and a poor prognosis. Pathological morphology and immunohistochemical marker combinations are needed for a definite diagnosis. However, the complexity of angiosarcomas' histological and cytological conformations and the overlap of pathological features with benign vascular tumors, sarcomas, and carcinomas pose difficulties in the differential diagnosis. Thus, the only effective ways to prolong survival are early detection and radical surgical resection.


Subject(s)
Humans , Male , Female , Middle Aged , Hemangiosarcoma , Ki-67 Antigen , Retrospective Studies , Biomarkers, Tumor/metabolism , Prognosis , Liver Neoplasms/pathology
9.
Chinese Journal of Pathology ; (12): 358-363, 2023.
Article in Chinese | WPRIM | ID: wpr-985680

ABSTRACT

Objective: To investigate the expression of glycoprotein non metastatic melanoma protein B (GPNMB) in renal eosinophilic tumors and to compare the value of GPNMB with CK20, CK7 and CD117 in the differential diagnosis of renal eosinophilic tumors. Methods: Traditional renal tumor eosinophil subtypes, including 22 cases of renal clear cell carcinoma eosinophil subtype (e-ccRCC), 19 cases of renal papillary cell carcinoma eosinophil subtype (e-papRCC), 17 cases of renal chromophobe cell carcinoma eosinophil subtype (e-chRCC), 12 cases of renal oncocytoma (RO) and emerging renal tumor types with eosinophil characteristics [3 cases of eosinophilic solid cystic renal cell carcinoma (ESC RCC), 3 cases of renal low-grade eosinophil tumor (LOT), 4 cases of fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and 5 cases of renal epithelioid angiomyolipoma (E-AML)], were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2017 to March 2022. The expression of GPNMB, CK20, CK7 and CD117 was detected by immunohistochemistry and statistically analyzed. Results: GPNMB was expressed in all emerging renal tumor types with eosinophil characteristics (ESC RCC, LOT, FH-dRCC) and E-AML, while the expression rates in traditional renal eosinophil subtypes e-papRCC, e-chRCC, e-ccRCC and RO were very low or zero (1/19, 1/17, 0/22 and 0/12, respectively); the expression rate of CK7 in LOT (3/3), e-chRCC (15/17), e-ccRCC (4/22), e-papRCC (2/19), ESC RCC (0/3), RO (4/12), E-AML(1/5), and FH-dRCC (2/4) variedly; the expression of CK20 was different in ESC RCC (3/3), LOT(3/3), e-chRCC(1/17), RO(9/12), e-papRCC(4/19), FH-dRCC(1/4), e-ccRCC(0/22) and E-AML(0/5), and so did that of CD117 in e-ccRCC(2/22), e-papRCC(1/19), e-chRCC(16/17), RO(10/12), ESC RCC(0/3), LOT(1/3), E-AML(2/5) and FH-dRCC(1/4). GPNMB had 100% sensitivity and 97.1% specificity in distinguishing E-AML and emerging renal tumor types (such as ESC RCC, LOT, FH-dRCC) from traditional renal tumor types (such as e-ccRCC, e-papRCC, e-chRCC, RO),respectively. Compared with CK7, CK20 and CD117 antibodies, GPNMB was more effective in the differential diagnosis (P<0.05). Conclusion: As a new renal tumor marker, GPNMB can effectively distinguish E-AML and emerging renal tumor types with eosinophil characteristics such as ESC RCC, LOT, FH-dRCC from traditional renal tumor eosinophil subtypes such as e-ccRCC, e-papRCC, e-chRCC and RO, which is helpful for the differential diagnosis of renal eosinophilic tumors.


Subject(s)
Humans , Kidney Neoplasms/pathology , Carcinoma, Renal Cell/pathology , Diagnosis, Differential , Angiomyolipoma/diagnosis , Biomarkers, Tumor/metabolism , Leukemia, Myeloid, Acute/diagnosis , Membrane Glycoproteins
10.
Chinese Journal of Lung Cancer ; (12): 385-395, 2022.
Article in Chinese | WPRIM | ID: wpr-939722

ABSTRACT

BACKGROUND@#Reticulosome family gene 1 (RTN1) is a reticulosome-encoding gene associated with the endoplasmic reticulum. RTN1 plays a key role in membrane trafficking or neuroendocrine secretion of neuroendocrine cells, while RTN1 serves as a potential diagnostic/therapeutic marker for neurological diseases and cancer. However, the expression of RTN1 and its effect on the immune microenvironment in patients with lung adenocarcinoma have not been reported. In this study, we aimed to investigate the expression of RTN1 in lung adenocarcinoma and its correlation with immune infiltration and survival in lung adenocarcinoma using public databases and bioinformatics network tools.@*METHODS@#Expression levels of RTN1 mRNA in tumor and normal tissues were analyzed using Tumor Immune Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2). RTN1 protein expression was examined using the Human Protein Atlas. The clinical prognostic significance of RTN1 was analyzed using the GEPIA2 plotter database. To further confirm the potential function of RTN1, the data were analyzed using gene set enrichment analysis. In addition, We performed dimensionality-reduced clustering analysis at the single-cell sequencing level on two datasets from the Tumor Immune Single-cell Hub (TISCH) database to observe the cellular clustering of RTN1 in different types of immune cells. Using the TIMER online tool to analyze and predict the infiltration abundance of different types of immune cells in the immune microenvironment of lung adenocarcinoma patients in the TCGA cohort; TIMER and CIBERSORT were used to study the relationship between genes co-expressed with RTN1 and its associated tumor-infiltrating immune cells; finally, TIMER was used to analyze the relationship between RTN1 and immune correlations between immune checkpoints.@*RESULTS@#We found that RTN1 expression was decreased in patients with lung adenocarcinoma and was closely related to patient prognosis. RTN1 is involved in the process of phagosome formation, hematopoietic cell formation and cell adhesion, and plays an important role in T cell activation. Using cBioPortal and TCGA data to analyze, it is found that RTN1 is significantly associated with BTK, CD4, ECSF1R, MNDA, NCKAP1L and SNX20. High expression of the above genes may cause significant upregulation of CD4+ T cells, mast cells, monocytes, myeloid dendritic cells and M1 macrophages. The expression of RTN1 is closely related to the common immune checkpoints CD274, CTLA4, HAVCR2, LAG3, PDCD1, PDCD1LG2, TIGIT and SIGLEC15 immune checkpoints.@*CONCLUSIONS@#RTN1 may act as a tumor suppressor gene and indicate better prognosis. Furthermore, RTN1 is associated with immune infiltration that may be involved in the immunotherapy response in LUAD. However, the related mechanism needs further research.


Subject(s)
Humans , Adenocarcinoma of Lung/pathology , Biomarkers, Tumor/metabolism , Gene Expression Profiling , Lung Neoplasms/pathology , Mast Cells/pathology , Membrane Proteins/metabolism , Nerve Tissue Proteins/genetics , Prognosis , Sorting Nexins/metabolism , Tumor Microenvironment/genetics
11.
Journal of Experimental Hematology ; (6): 778-783, 2022.
Article in Chinese | WPRIM | ID: wpr-939688

ABSTRACT

OBJECTIVE@#To investigate the expression of PD-L1 and PD-1 in pathological tissue of patients newly diagnosed with diffuse large B-cell lymphoma (DLBCL).@*METHODS@#Data of DLBCL patients who visited the Department of Hematology, Peking University Third Hospital from May 2014 to March 2017 were collected, and a total of 21 patients with pathological tissue sections which were still available at the initial treatment were selected. The patients were divided into complete remission (CR) group and refractory relapse (RR) group according to clinical outcome. The expression and proportion of PD-1 and PD-L1 in pathological tissue sections were detected by multiplex fluorescence immunohistochemical staining, and the differences in the expression of different molecular markers in different clinical characteristics and different prognosis were compared using non-parametric test.@*RESULTS@#The ratio of PD-L1+ cells to PD-1+ cells (PD-L1+ : PD-1+) was 5.14±3.825 in increased lactate dehydrogenase (LDH) group, which was significantly higher than 0.76±0.563 in non-increased LDH group (P=0.001). The ratio of PD-L1+ : PD-1+ in increased Treg cells group was 1.41±1.454, which was lower than 6.42±4.426 in decreased Treg cells group (P=0.023).@*CONCLUSION@#The increased expression ratio of PD-L1 to PD-1 in pathological tissue sections of newly diagnosed DLBCL patients is associated with poor prognostic clinical characteristics.


Subject(s)
Humans , B7-H1 Antigen/metabolism , Biomarkers, Tumor/metabolism , Lymphoma, Large B-Cell, Diffuse/pathology , Neoplasm Recurrence, Local , Prognosis , Programmed Cell Death 1 Receptor/metabolism
12.
Frontiers of Medicine ; (4): 322-338, 2022.
Article in English | WPRIM | ID: wpr-939882

ABSTRACT

Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.


Subject(s)
Humans , Male , Antigens, Neoplasm/chemistry , Biomarkers, Tumor/metabolism , Glycosylation , Hematologic Neoplasms/drug therapy , Immunotherapy, Adoptive/methods , Neoplasm Recurrence, Local/metabolism , Receptors, Chimeric Antigen , T-Lymphocytes , United States
13.
Journal of Southern Medical University ; (12): 681-689, 2022.
Article in Chinese | WPRIM | ID: wpr-936363

ABSTRACT

OBJECTIVE@#To assess the value of m7G-lncRNAs in predicting the prognosis and microenvironment of colorectal cancer (CRC).@*METHODS@#We screened m7G-lncRNAs from TCGA to construct an m7G-lncRNAs risk model using multivariate Cox analysis, which was validated using ROC and C-index curves. Calibration and nomogram were used to predict the prognosis of CRC patients. Point-bar charts and K-M survival curves were used to assess the correlation of risk scores with the patients' clinical staging and prognosis. CIBERSORT and ESTIMATE were used to explore the association between the tumor microenvironment and immune cell infiltration in patients in high and low risk groups and the correlation of risk scores with microsatellite instability, stem cell index and immune checkpoint expression. A protein-protein interaction network was constructed, and the key targets regulated by m7G-lncRNAs were identified and validated in paired samples of CRC and adjacent tissues by immunoblotting.@*RESULTS@#We identified a total of 1722 m7G-lncRNAs from TCGA database, from which 12 lncRNAs were screened to construct the risk model. The AUCs of the risk model for predicting survival outcomes at 1, 3 and 5 years were 0.727, 0.747 and 0.794, respectively. The AUC of the nomogram for predicting prognosis was 0.794, and the predicted results were consistent with actual survival outcomes of the patients. The patients in the high-risk group showed more advanced tumor stages and a greater likelihood of high microsatellite instability than those in the low-risk group (P < 0.05). The tumor stemness index was negatively correlated with the risk score (r=-0.19; P=7.3e-05). Patients in the high-risk group had higher stromal cell scores (P=0.0028) and higher total scores (P=0.007) with lowered expressions of activated mast cells (r=-0.11; P=0.045) and resting CD4+ T cells (r=-0.14; P=0.01) and increased expressions of most immune checkpoints (P < 0.05). ATXN2 (P= 0.006) and G3BP1 (P=0.007) were identified as the key targets regulated by m7G-lncRNAs, and their expressions were both higher in CRC than in adjacent tissues.@*CONCLUSION@#The risk model based on 12 m7G-lncRNAs has important prognostic value for CRC and can reflect the microenvironment and the efficacy of immunotherapy in the patients.


Subject(s)
Humans , Biomarkers, Tumor/metabolism , Colonic Neoplasms , DNA Helicases/metabolism , Gene Expression Regulation, Neoplastic , Microsatellite Instability , Poly-ADP-Ribose Binding Proteins/metabolism , Prognosis , RNA Helicases/metabolism , RNA Recognition Motif Proteins/metabolism , RNA, Long Noncoding/metabolism , Tumor Microenvironment
14.
Journal of Southern Medical University ; (12): 123-129, 2022.
Article in Chinese | WPRIM | ID: wpr-936293

ABSTRACT

OBJECTIVE@#To assess the value of DNA methylation level of HYAL2 gene as a molecular marker for differential diagnosis of malignant and benign thyroid tumors.@*METHODS@#DNA methylation of HYAL2 gene in tissue specimens of 190 patients with papillary thyroid cancer (PTC) and 190 age- and gender-matched patients with benign thyroid tumors was examined by mass spectrometry, and the protein expression of HYAL2 was detected immunohistochemically for another 55 pairs of patients. Logistic regression analysis was performed to calculate the odds ratio (OR) and evaluate the correlation of per 10% reduction in DNA methylation with PTC. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) was calculated to assess the predictive value of alterations in HYAL2 methylation.@*RESULTS@#Hypomethylation of HYAL2_CpG_3 was significantly correlated with early-stage PTC (OR=1.51, P=0.001), even in stage I cancer (OR=1.42, P=0.007). Age-stratified analysis revealed a significantly stronger correlation between increased HYAL2_CpG_ 3 methylation and early-stage PTC in patients below 50 years than in those older than 50 years (OR: 1.89 vs 1.37, P < 0.05); ROC analysis also showed a larger AUC of 0.787 in younger patients. The results of immunohistochemistry showed that patients with PTC had significantly higher protein expressions of HYAL2 than patients with benign tumors.@*CONCLUSION@#The alterations of DNA methylation level of HYAL2 gene is significantly correlated with early-stage PTC, suggesting the value of DNA methylation level as a potential biomarker for differentiation of malignant from benign thyroid tumors.


Subject(s)
Humans , Middle Aged , Adenoma, Oxyphilic/genetics , Biomarkers, Tumor/metabolism , Cell Adhesion Molecules/metabolism , DNA Methylation , GPI-Linked Proteins/metabolism , Hyaluronoglucosaminidase/metabolism , Immunohistochemistry , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/pathology
15.
Chinese Journal of Pathology ; (12): 437-443, 2022.
Article in Chinese | WPRIM | ID: wpr-935559

ABSTRACT

Objective: To study the clinicopathological features, immunophenotype, molecular changes, differential diagnosis and prognosis of eosinophilic vacuolated tumor (EVT) of the kidney. Methods: Four cases were collected retrospectively from 2014 to 2020 at Ningbo Diagnostic Pathology Center. The clinicopathologic features and immunophenotypic profile were studied by light microscopy and immunohistochemistry. Targeted next-generation sequencing (NGS) panel was used to detect cancer-associated mutation. Follow-up and literature review were also performed. Results: Among the 4 patients studied,2 were males and 2 were females. The age of the patients ranged from 44 to 63 years (the mean age: 51 years).Tumor size ranged from 1.5 to 4.2 cm (mean: 2.3 cm). Microscopically, tumors were well-circumscribed, unencapsulated. Thick-walled vessels and entrapped renal tubules were found within or at the periphery of the tumors. The tumors were predominantly composed of nest pattern, and focal tubular pattern. The tumor cells exhibited abundant, eosinophilic, granular cytoplasm and conspicuous, large nucleoli. Prominent intracytoplasmic vacuoles were seen. These cytoplasmic vacuoles varied in size and frequently coalesced into a large space. Loose fibromatous or hyaline stroma was focally noted. Immunohistochemically, the tumor cells in all cases exhibited a CD117+/CK7-phenotype. All cases were positive for CD10 and p504s. MTOR, S6 and cathepsin K were positive in 4 cases. TFE3, CA9, Melan A and HMB45 were negative in all cases. SDHB retained expression. NGS demonstrated MTOR mutations in all cases, and TSC2 mutation in 2 cases. Conclusions: EVT is a rarely oncocytic renal tumor with unique morphology, immunohistochemical phenotype, molecular profile and an indolent behavior. Recognition of the characteristics of this novel but rare entity will allow for better classification of renal tumors.


Subject(s)
Female , Humans , Male , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/pathology , Kidney/pathology , Kidney Neoplasms/pathology , Retrospective Studies , TOR Serine-Threonine Kinases/genetics
16.
Chinese Journal of Pathology ; (12): 419-424, 2022.
Article in Chinese | WPRIM | ID: wpr-935556

ABSTRACT

Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3+T cells were deficient in 124 cases (124/192, 66.31%). CD8+T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8+T cells were positively correlated with CD3+T cells (P=0.032), MHC-Ⅰ expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.


Subject(s)
Humans , Adenocarcinoma/pathology , B7-H1 Antigen/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Pancreatic Ductal/pathology , Inflammation/pathology , Lymphocytes, Tumor-Infiltrating/metabolism , Pancreatic Neoplasms/pathology , Prognosis , Tumor Microenvironment
17.
Chinese Journal of Oncology ; (12): 268-275, 2022.
Article in Chinese | WPRIM | ID: wpr-935210

ABSTRACT

Objective: To investigate the expression of cortactin in colorectal cancer and its correlation with clinicopathological parameters and prognosis. Methods: The expressions of cortactin in normal colorectal mucosal tissue and colorectal cancer tissue in paraffin-embedded tissue microarray from 319 patients who were diagnosed as colorectal cancer and treated in Cancer Hospital of Chinese Academy of Medical Sciences from 2006 to 2009 was detected by immunohistochemistry. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox proportional risk regression model was used for multivariate analysis. Results: The positive expression rates of cortactin in colorectal cancer tissue and normal colorectal mucosal tissue were 61.1% (195/319) and 5.6% (18/319, P<0.001), respectively. T-stage, N-stage, American Joint Committee on Cancer (AJCC) stage, degree of tumor differentiation, neural invasion and preoperative carcinoembryonic antigen (CEA) levels were associated with the expression of cortactin (P<0.05). The positive expression of cortactin was associated with poorer disease-free survival (P=0.036) and overall survival (P=0.043), and the effect was more significant in patients with stage Ⅱ to Ⅲ. For patients with stage Ⅱ-Ⅲ colorectal cancer, postoperative adjuvant therapy was associated with disease-free survival (P=0.007) and overall survival (P=0.015). The vascular tumor embolus, pathological type, preoperative CEA level and cortactin expression were independent influencing factors for disease-free survival (P<0.05). The age, AJCC stage, preoperative CEA level and cortactin expression were independent influencing factors for overall survival (P<0.05). Preoperative CEA level and cortactin expression were independent influencing factors for disease-free survival and overall survival (P<0.05). Conclusion: Cortactin is expressed in colorectal cancer and in stage Ⅱ-Ⅲ patients, it is a potential predictor of colorectal cancer prognosis.


Subject(s)
Humans , Biomarkers, Tumor/metabolism , Carcinoembryonic Antigen/metabolism , Colorectal Neoplasms/pathology , Cortactin/metabolism , Prognosis , Retrospective Studies
18.
Chinese Journal of Lung Cancer ; (12): 303-310, 2022.
Article in Chinese | WPRIM | ID: wpr-928813

ABSTRACT

BACKGROUND@#The expression of programmed cell death ligand 1 (PD-L1) as a biomarker for immunotherapy in non-small cell lung cancer (NSCLC) is routinely detected in clinical pathology department. However, the spatial heterogeneity of PD-L1 expression in intrapulmonary tumors and extrapulmonary metastases is still a challenge for the clinical testing. This study aims to explore the differences of PD-L1 expression in test samples obtaining from different sites of NSCLC. This study may contribute to the detection strategy of PD-L1 in patients with advanced lung cancer.@*METHODS@#One hundred and thirty-one cases of consecutively detected PD-L1 (22c3 assay, Dako) staining in metastatic NSCLC and 972 cases of non-paired intrapulmonary NSCLC were collected. The discrepancies of tumor proportion score (TPS) of PD-L1 expression in intrapulmonary samples and extrapulmonary metastatic samples of different sites were compared.@*RESULTS@#The positive expression rate of PD-L1 in extrapulmonary metastatic NSCLC (TPS ≥ 1%) was 61.83%, and the TPS was significantly higher than that in intrapulmonary tumors (P=0.03). The PD-L1 scores of the specimens obtained from different sites were significantly different (P=0.007). The positive rates of PD-L1 in liver and adrenal metastases were 85.71% and 77.78% respectively, and their TPS were significantly higher than that of the intrapulmonary samples (P<0.05). The positive rates of PD-L1 in lymph node, bone, brain, soft tissue, and pleural metastases was 40.00%-66.67%, with no significant differences compared to intrapulmonary tumors. The analysis of histological subtype and sample type showed that the PD-L1 score of extrapulmonary samples of adenocarcinoma subtype or surgical specimen was significantly higher than that of intrapulmonary tumors. The analysis of clinicopathological parameters showed that the PD-L1 positive expression or high expression were significantly correlated with male patients, smoking history, and epidermal growth factor receptor (EGFR) wild type.@*CONCLUSIONS@#The expression of PD-L1 in metastatic NSCLC is generally higher than that in intrapulmonary tumor, and the positive rate of PD-L1 expression was discrepant in different sites of specimen. The differences of PD-L1 score between extrapulmonary metastatic samples and intrapulmonary samples may be associated with different metastatic sites, histological subtype, and specimen type.


Subject(s)
Humans , Male , B7-H1 Antigen/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Immunohistochemistry , Lung Neoplasms/drug therapy
19.
Arq. gastroenterol ; 58(1): 55-60, Jan.-Mar. 2021. tab, graf
Article in English | LILACS | ID: biblio-1248983

ABSTRACT

ABSTRACT BACKGROUND: Colorectal cancer is the third most common neoplasm in the world. Methylation of tumor related genes in CpG islands can cause gene silencing and been involved in the development of cancer. The potential role of DKK2 as a biomarker for early diagnosis of colorectal cancer remains unclear. OBJECTIVE: The aim of the study was to evaluate the profile of methylation and RNAm expression of DKK2 as potential predictors of colorectal cancer diagnosis and prognosis. METHODS: Expression of mRNAs encoding DKK2 in 35 colorectal cancer tissues was quantified using real-time polymerase chain reaction analysis. The DNA methylation was studied by high resolution melting analysis. The general characteristics of the patients were collected. DKK2 methylation and expression were compared to clinical, pathological aspects and overall survival. RESULTS: Among the 35 patients studied, 18 were male, 10 were on right colon and 25 on left colon. Among the 20 patients with high hypermethylation, 15 of them had mRNA low expression of DKK2. There was no significant association between DKK2 promoter methylation and mRNA DKK2 expression and clinical or pathological features. DKK2 promoter methylation (P=0.154) and DKK2 RNA expression (P=0.345) did not show significant correlation with overall survival. CONCLUSION: DKK2 promoter methylation and DKK2 RNA status appear to be biomarkers of cancer diagnosis but not predictors of prognosis.


RESUMO CONTEXTO: O câncer colorretal é a terceira neoplasia mais comum no mundo. A metilação de alguns genes nas ilhas CpG podem causar silenciamento gênico e estar envolvida no desenvolvimento de câncer. O potencial papel de DKK2 como um biomarcador no diagnóstico precoce de CCR permanece incerto. OBJETIVO: O objetivo do estudo foi avaliar o perfil de metilação e expressão de RNAm do gene DKK2 para identificar preditores potenciais de diagnóstico e prognóstico de CCR. MÉTODOS: A expressão de mRNAs que codificam DKK2 em 35 tecidos de câncer colorretal foi quantificada por reação em cadeia da polimerase em tempo real e a metilação do DNA foi verificada por análise de alta resolução. As características gerais dos pacientes foram coletadas. A metilação e expressão de DKK2 foram comparadas aos aspectos clínicos, patológicos e à sobrevida global. RESULTADOS: Entre os 35 pacientes estudados, 18 eram do sexo masculino, 10 tumores eram do cólon ascendente ou transverso e 25 do descendente ou reto. Entre os 20 pacientes com hipermetilação, 12 deles apresentaram baixa expressão de RNAm do gene DKK2. Não houve associação significativa entre a metilação do promotor de DKK2 e a expressão de RNAm de DKK2 e características clínicas ou patológicas. A metilação do promotor de DKK2 e a expressão do RNA de DKK2 não mostraram correlação com sobrevida global dos pacientes com CCR. CONCLUSÃO: A metilação do gene promotor e a expressão do RNAm do gene DKK2 parecem ser biomarcadores de diagnóstico de câncer, mas não se mostraram úteis na avaliação prognóstica.


Subject(s)
Humans , Male , Female , Colorectal Neoplasms/genetics , DNA Methylation , Prognosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Promoter Regions, Genetic , CpG Islands , Intercellular Signaling Peptides and Proteins/genetics
20.
J. coloproctol. (Rio J., Impr.) ; 41(1): 63-69, Jan.-Mar. 2021. tab, graf
Article in English | LILACS | ID: biblio-1286971

ABSTRACT

Abstract Objective Type-I collagen (Col-I) is one of the main macromolecules of the extracellular matrix, and it is involved in the desmoplastic stromal reaction, an indicator of worse prognosis in cases of colorectal cancer (CRC). The purpose of the present study was to investigate Col-I expression in cases of CRC and adenoma and to correlate with the clinical data and the data regarding the lifestyle of the patients. Methods A retrospective study including 22 patients with adenoma and 15 with CRC treated at a coloproctology service. The clinical and lifestyle data were obtained through medical records, and Col-I expression was investigated by immunohistochemistry. Results Women represented most cases of adenoma (63.64%), whereas CRC was found mainly in men (73.33%) (p=0.0448). Immunoexpression of Col-I showed a basement membrane thickening in areas of lining of epithelium and around the glands in both lesions. The cases of CRC had a quite evident fibrosis process in the stroma. The quantitative analysis demonstrated a higher protein expression in CRCs compared to adenomas (p=0.0109), as well as in female patients (p=0.0214), patients aged ≥ 50 years (p=0.0400), and in those with a positive family history of colorectal disease (p=0.0292). These results suggested a remodeling of the microenvironment of the Worked developed at the Department of Morphology, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, ES, Brazil. Conclusion The immunohistochemical analysis encourages the performance of more comprehensive studies to ascertain if our results could be a tool for the diagnosis and monitoring of the patients.


Resumo Objetivo O colágeno tipo I (Col-I) é uma das principais macromoléculas da matriz extracelular, e está envolvido na reação desmoplástica estromal, um indicador de pior prognóstico em casos de câncer colorretal (CCR). O objetivo foi investigar a expressão do Col-I emcasos de CCR e adenoma, e correlacioná-la comdados clínicos e de estilo de vida dos pacientes. Metodologia Foi realizado umestudoretrospectivo com22pacientes comadenoma e 15 comCCR tratadosemumserviço de coloproctologia.Os dados dos pacientes foramobtidos dos prontuários médicos, e a expressão do Col-I foi investigada por imunohistoquímica. Resultados As mulheres representaram a maioria dos casos de adenomas (63,64%), enquanto o CCR (73,33%) (p=0,0448) foi mais comum entre os homens. A imunoexpressão de Col-I mostrou espessamento da membrana basal em áreas de revestimento do epitélio e em volta de glândulas em ambas as lesões. O CCR apresentou fibrose no estroma. As análises quantitativas demonstraram maior expressão proteica no CCR (p=0,0109), assim como em mulheres (p=0,0214), pacientes com idade ≥ 50 anos (p=0,0400), e em pacientes com histórico positivo de doença colorretal na família (p=0,0292). Estes resultados sugerem a remodelação do microambiente tumoral na carcinogênese do CCR. As correlações clínico-patológicas positivas mostram uma ligação plausível entre o perfil do paciente e os achados imunohistoquímcos, o que indica uma possível forma de estratificação dos pacientes. Conclusão As análises imunohistoquímicas estimulam a execução de estudos mais abrangentes para confirmar se nossos resultados poderão ser uma ferramenta para o diagnóstico e o monitoramento dos pacientes.


Subject(s)
Humans , Male , Female , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Adenocarcinoma/diagnosis , Biomarkers, Tumor/metabolism , Gene Expression Regulation, Neoplastic , Collagen Type I/genetics , Extracellular Matrix/metabolism , Tumor Microenvironment/immunology
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