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1.
Chinese Journal of Oncology ; (12): 767-775, 2022.
Article in Chinese | WPRIM | ID: wpr-940937

ABSTRACT

Objective: To investigate the value of predicting the degree of differentiation of pulmonary invasive adenocarcinoma (IAC) based on CT image radiomics model and the expression difference of immunohistochemical factors between different degrees of differentiation of lesions. Methods: The clinicopathological data of patients with pulmonary IAC confirmed by surgical pathology in the Affiliated Huai'an First People's Hospital to Nanjing Medical University from December 2017 to September 2018 were collected. High-throughput feature acquisition was performed for all outlined regions of interest, and prediction models were constructed after dimensionality reduction by the minimum absolute shrinkage operator. Receiver operating characteristic curve was used to assess the predictive efficacy of clinical characteristic model, radiomics model and individualized prediction model combined with both to identify the degree of pulmonary IAC differentiation, and immunohistochemical expressions of Ki-67, NapsinA and TTF-1 were compared between groups with different degrees of IAC differentiation using rank sum test. Results: A total of 396 high-throughput features were extracted from all IAC lesions, and 10 features with high generalization ability and correlation with the degree of IAC differentiation were screened. The mean radiomics score of poorly differentiated IAC in the training group (1.206) was higher than that of patients with high and medium differentiation (0.969, P=0.001), and the mean radiomics score of poorly differentiated IAC in the test group (1.545) was higher than that of patients with high and medium differentiation (-0.815, P<0.001). The differences in gender (P<0.001), pleural stretch sign (P=0.005), and burr sign (P=0.033) were statistically significant between patients in the well and poorly differentiated IAC groups. Multifactorial logistic regression analysis showed that gender and pleural stretch sign were related to the degree of IAC differentiation (P<0.05). The clinical feature model consisted of age, gender, pleural stretch sign, burr sign, tumor vessel sign, and vacuolar sign, and the individualized prediction model consisted of gender, pleural stretch sign, and radiomic score, and was represented by a nomogram. The Akaike information standard values of the radiomics model, clinical feature model and individualized prediction model were 54.756, 82.214 and 53.282, respectively. The individualized prediction model was most effective in identifying the degree of differentiation of pulmonary IAC, and the area under the curves (AUC) of the individualized prediction model in the training group and the test group were 0.92 (95% CI: 0.86-0.99) and 0.88 (95% CI: 0.74-1.00, respectively). The AUCs of the radiomics group model for predicting the degree of differentiation of pulmonary IAC in the training group and the test group were 0.91 (95% CI: 0.83-0.98) and 0.87 (95% CI: 0.72-1.00), respectively. The AUCs of the clinical characteristics model for predicting the degree of differentiation of pulmonary IACs in the training and test groups were 0.75 (95% CI: 0.63-0.86) and 0.76 (95% CI: 0.59-0.94), respectively. The expression level of Ki-67 in poorly differentiated IAC was higher than that in well-differentiated IAC (P<0.001). The expression levels of NapsinA, TTF-1 in poorly differentiated IAC were higher than those in well-differentiated IAC (P<0.05). Conclusions: Individualized prediction model consisted of gender, pleural stretch sign and radiomics score can discriminate the differentiation degree of IAC with the best performance in comparison with clinical feature model and radiomics model. Ki-67, NapsinA and TTF-1 express differently in different degrees of differentiation of IAC.


Subject(s)
Adenocarcinoma of Lung/pathology , Humans , Ki-67 Antigen , Lung Neoplasms/pathology , Retrospective Studies , Tomography, X-Ray Computed/methods
2.
Chinese Journal of Oncology ; (12): 555-561, 2022.
Article in Chinese | WPRIM | ID: wpr-940922

ABSTRACT

Objective: Solid and micropapillary pattern are highly invasive histologic subtypes in lung adenocarcinoma and are associated with poor prognosis while the biopsy sample is not enough for the accurate histological diagnosis. This study aims to assess the correlation and predictive efficacy between metabolic parameters in (18)F-fluorodeoxy glucose positron emission tomography/computed tomography ((18)F-FDG PET-CT), including the maximum SUV (SUV(max)), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and solid and micropapillary histological subtypes in lung adenocarcinoma. Methods: A total of 145 resected lung adenocarcinomas were included. The clinical data and preoperative (18)F-FDG PET-CT data were retrospectively analyzed. Mann-Whitney U test was used for the comparison of the metabolic parameters between solid and micropapillary subtype group and other subtypes group. Receiver operating characteristic (ROC) curve and areas under curve (AUC) were used for evaluating the prediction efficacy of metabolic parameters for solid or micropapillary patterns. Univariate and multivariate analyses were conducted to determine the prediction factors of the presence of solid or micropapillary subtypes. Results: Median SUV(max) and TLG in solid and papillary predominant subtypes group (15.07 and 34.98, respectively) were significantly higher than those in other subtypes predominant group (6.03 and 10.16, respectively, P<0.05). ROC curve revealed that SUV(max) and TLG had good efficacy for prediction of solid and micropapillary predominant subtypes [AUC=0.811(95% CI: 0.715~0.907) and 0.725(95% CI: 0.610~0.840), P<0.05]. Median SUV(max) and TLG in lung adenocarcinoma with the solid or micropapillary patterns (11.58 and 22.81, respectively) were significantly higher than those in tumors without solid and micropapillary patterns (4.27 and 6.33, respectively, P<0.05). ROC curve revealed that SUV(max) and TLG had good efficacy for predicting the presence of solid or micropapillary patterns [AUC=0.757(95% CI: 0.679~0.834) and 0.681(95% CI: 0.595~0.768), P<0.005]. Multivariate logistic analysis showed that the clinical stage (Stage Ⅲ-Ⅳ), SUV(max) ≥10.27 and TLG≥7.12 were the independent predictive factors of the presence of solid or micropapillary patterns (P<0.05). Conclusions: Preoperative SUV(max) and TLG of lung adenocarcinoma have good prediction efficacy for the presence of solid or micropapillary patterns, especially for the solid and micropapillary predominant subtypes and are independent factors of the presence of solid or micropapillary patterns.


Subject(s)
Adenocarcinoma of Lung/diagnostic imaging , Fluorodeoxyglucose F18/metabolism , Humans , Lung Neoplasms/pathology , Multimodal Imaging/methods , Positron Emission Tomography Computed Tomography , Positron-Emission Tomography/methods , Prognosis , Radiopharmaceuticals , Retrospective Studies , Tomography, X-Ray Computed/methods , Tumor Burden
3.
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)
Adenocarcinoma of Lung/pathology , Biomarkers, Tumor/metabolism , Gene Expression Profiling , Humans , Lung Neoplasms/pathology , Mast Cells/pathology , Membrane Proteins/metabolism , Nerve Tissue Proteins/genetics , Prognosis , Sorting Nexins/metabolism , Tumor Microenvironment/genetics
4.
Chinese Journal of Oncology ; (12): 321-325, 2022.
Article in Chinese | WPRIM | ID: wpr-935215

ABSTRACT

Pulmonary enteric adenocarcinoma (PEAC), as a rare histologic subtype of primary lung adenocarcinoma, is defined as an adenocarcinoma in which the enteric component exceeds 50%. It is named after its shared morphological and immunohistochemical features with colorectal cancer. While with such similarity, the differential diagnosis of PEAC and lung metastatic colorectal cancer is a great challenge in the clinic. PEAC may originate from the intestinal metaplasia of respiratory basal cells stimulated by risk factors such as smoking. Current studies have found that KRAS is a relatively high-frequency mutation gene, and other driver gene mutations are rare. In terms of immunohistochemistry, in pulmonary enteric adenocarcinoma, the positive rate was 88.2% (149/169) for CK7, 78.1% (132/169) for CDX2, 48.2% (82/170) for CK20 and 38.8% (66/170) for TTF1. As for clinical features, the average age of onset for pulmonary enteric adenocarcinoma was 62 years, male patients accounted for 56.5% (35/62), smokers accounted for 78.8% (41/52), and 41.4% (24/58) of the primary lesion was located in the upper lobe of the right lung. In terms of treatment, conventional non-small cell lung cancer (NSCLC) regimens rather than colorectal cancer regimens are now recommended. There is still an urgent need for more basic and clinical research, in-depth exploration of its molecular feature and pathogenesis from the level of omics and other aspects, to help diagnosis and differential diagnosis, and find the optimal chemotherapy regimen, possibly effective targeted therapy and even immunotherapy.


Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma of Lung/pathology , Biomarkers, Tumor , Carcinoma, Non-Small-Cell Lung/diagnosis , Colonic Neoplasms/pathology , Diagnosis, Differential , Humans , Lung Neoplasms/genetics , Male , Middle Aged
5.
Chinese Journal of Lung Cancer ; (12): 311-322, 2022.
Article in Chinese | WPRIM | ID: wpr-928814

ABSTRACT

BACKGROUND@#m6A RNA methylation modification plays an important role in the occurrence and progression of lung cancer and regulates tumor immunity. Current studies mostly focus on the differential expression of some specific m6A effectors and infiltrating immune cell. m6A methylation modification is the result of mutual adjustment and balance between effectors, and changes in the expression of one or two effectors are far from enough to reflect the panorama of m6A methylation. The role of m6A in the immune microenvironment of lung adenocarcinoma (LUAD) is still poorly understood. The aim of this study is to investigate the effect of different m6A modification patterns in immune microenvironment of LUAD.@*METHODS@#LUAD data was obtained from The Cancer Genome Atlas (TCGA), University of California Santa Cruz Xena (UCSC Xena) and Gene Expression Omnibus (GEO) databases. Gene mutation, differential expression and survival analysis were performed for 24 m6A effectors. The m6A modification pattern was constructed by unsupervised clustering method, and the m6A clusters survival analysis, gene set variation analysis, immune score and immune cell infiltration analysis were performed. The association between LRPPRC protein expression levels and infiltration of CD8+ cytotoxic T lymphocytes and CD68+ macrophages in the tumor microenvironment was validated by immunohistochemistry in LUAD tissue microarray with 68 cases.@*RESULTS@#The mutations of m6A effector were found in 150 of 567 LUAD cases with a frequency of 26.46%. 6 readers and 3 writers were significantly up regulated in LUAD tissues compared with normal tissues. IGF2BP1 and HNRNPC are the independent risk factors for prognosis of LUAD. Abundant cross-talks among writers, erasers and readers were demonstrated. Three m6A modification patterns with different immune cell infiltration characteristics and clinical prognosis were established. Among m6A effectors, LRPPRC was found to be inversely associated with the infiltration of CD8+ cytotoxic T lymphocytes and CD68+ macrophages, and was validated in 68 LUAD tissues.@*CONCLUSIONS@#m6A modification patterns play non-negligible roles in regulating the immune microenvironment. LRPPRC has potential to be a new biomarker for checkpoint inhibitor immunotherapy.


Subject(s)
Adenocarcinoma/genetics , Adenocarcinoma of Lung/pathology , Adenosine/metabolism , Gene Expression Regulation, Neoplastic , Humans , Lung Neoplasms/pathology , Methylation , Tumor Microenvironment/genetics
6.
Chinese Journal of Lung Cancer ; (12): 245-252, 2022.
Article in Chinese | WPRIM | ID: wpr-928805

ABSTRACT

BACKGROUND@#Lung cancer is the cancer with the highest mortality at home and abroad at present. The detection of lung nodules is a key step to reducing the mortality of lung cancer. Artificial intelligence-assisted diagnosis system presents as the state of the art in the area of nodule detection, differentiation between benign and malignant and diagnosis of invasive subtypes, however, a validation with clinical data is necessary for further application. Therefore, the aim of this study is to evaluate the effectiveness of artificial intelligence-assisted diagnosis system in predicting the invasive subtypes of early‑stage lung adenocarcinoma appearing as pulmonary nodules.@*METHODS@#Clinical data of 223 patients with early-stage lung adenocarcinoma appearing as pulmonary nodules admitted to the Lanzhou University Second Hospital from January 1st, 2016 to December 31th, 2021 were retrospectively analyzed, which were divided into invasive adenocarcinoma group (n=170) and non-invasive adenocarcinoma group (n=53), and the non-invasive adenocarcinoma group was subdivided into minimally invasive adenocarcinoma group (n=31) and preinvasive lesions group (n=22). The malignant probability and imaging characteristics of each group were compared to analyze their predictive ability for the invasive subtypes of early-stage lung adenocarcinoma. The concordance between qualitative diagnostic results of artificial intelligence-assisted diagnosis of the invasive subtypes of early-stage lung adenocarcinoma and postoperative pathology was then analyzed.@*RESULTS@#In different invasive subtypes of early-stage lung adenocarcinoma, the mean CT value of pulmonary nodules (P<0.001), diameter (P<0.001), volume (P<0.001), malignant probability (P<0.001), pleural retraction sign (P<0.001), lobulation (P<0.001), spiculation (P<0.001) were significantly different. At the same time, it was also found that with the increased invasiveness of different invasive subtypes of early-stage lung adenocarcinoma, the proportion of dominant signs of each group gradually increased. On the issue of binary classification, the sensitivity, specificity, and area under the curve (AUC) values of the artificial intelligence-assisted diagnosis system for the qualitative diagnosis of invasive subtypes of early-stage lung adenocarcinoma were 81.76%, 92.45% and 0.871 respectively. On the issue of three classification, the accuracy, recall rate, F1 score, and AUC values of the artificial intelligence-assisted diagnosis system for the qualitative diagnosis of invasive subtypes of early-stage lung adenocarcinoma were 83.86%, 85.03%, 76.46% and 0.879 respectively.@*CONCLUSIONS@#Artificial intelligence-assisted diagnosis system could predict the invasive subtypes of early‑stage lung adenocarcinoma appearing as pulmonary nodules, and has a certain predictive value. With the optimization of algorithms and the improvement of data, it may provide guidance for individualized treatment of patients.


Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma of Lung/pathology , Artificial Intelligence , Humans , Lung Neoplasms/pathology , Multiple Pulmonary Nodules , Neoplasm Invasiveness , Retrospective Studies
7.
Chinese Journal of Lung Cancer ; (12): 236-244, 2022.
Article in Chinese | WPRIM | ID: wpr-928804

ABSTRACT

BACKGROUND@#Lung cancer is still the malignant tumor with the highest morbidity and mortality in China. Lung adenocarcinoma is the most common subtype, and the number of lung cancer presenting as mixed ground glass nodule (mGGN) in imaging is gradually increasing. Visceral pleural invasion (VPI) is an important factor affecting the prognosis of mGGN type lung adenocarcinoma. The aim of the study is to explore and analyze the risk factors for VPI in mGGN type lung adenocarcinoma.@*METHODS@#From November 2016 to November 2019, 128 patients with mGGN lung adenocarcinoma underwent radical surgical resection in the First Affiliated Hospital of Nanjing Medical University. Their clinical data, including imaging, pathological and biological features, were collected and analyzed retrospectively. There were 40 males and 88 females, aged 60.3±9.3 years ranging from 30 to 81 years. Single factor Chi-square test and multivariate Logistic regression were used to analyze the risk factors of VPI in mGGN type lung adenocarcinoma.@*RESULTS@#Among 128 mGGN patients who met the inclusion criteria, 57 cases were pathologically confirmed with pleural invasion. Between the VPI (+) and VPI (-) group (P<0.05), there were significant differences in gender, maximum diameter of solid component, consolidation tumor ratio (CTR), spicule sign, history of lung disease, family history of hypertension, relation of lesion to pleura (RLP), coursing relationship between bronchi and nodules. In multivariate Logistic regression analysis, RLP (OR=3.529, 95%CI: 1.430-8.713, P=0.006) and coursing relationship between bronchi and nodules (OR=3.993, 95%CI: 1.517-10.51, P=0.005) were found to be independent risk factors for VPI (P<0.05).@*CONCLUSIONS@#The possibility of VPI in m GGN lung adenocarcinoma should be evaluated by combining these parameters in clinical diagnosis and treatment. As independent risk factors, RLP and coursing relationship between bronchi and nodules are instructive to identify VPI in mGGN type lung adenocarcinoma.


Subject(s)
Adenocarcinoma of Lung/pathology , Female , Humans , Lung Neoplasms/surgery , Male , Neoplasm Invasiveness , Pleura/pathology , Retrospective Studies , Risk Factors
8.
Chinese Journal of Lung Cancer ; (12): 156-166, 2022.
Article in Chinese | WPRIM | ID: wpr-928793

ABSTRACT

BACKGROUND@#Malignant pleural effusion is one of the common clinical manifestations of patients with lung adenocarcinoma. Patients with pleural effusion at the initial diagnosis of lung adenocarcinoma usually indicate poor prognosis. Epidermal growth factor receptor (EGFR) mutations mainly occur in patients with lung adenocarcinoma. Patients with different mutant subtypes have different prognosis. The clinical characteristics and prognostic factors of patients with EGFR mutated lung adenocarcinoma of different molecular subtypes combined with pleural effusion at initial diagnosis are still unclear. This study was designed to explore the clinical characteristics and prognostic factors of these patients in order to provide management recommendations for them.@*METHODS@#A retrospective analysis of the clinical characteristics, treatment, outcomes and progression-free survival (PFS) of first-line treatment in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis admitted to Department of Medical Oncology and Radiation Sickness, Peking University Third Hospital from January 2012 to June 2021 was performed. Pearson's chi-square test or Fisher's exact test were performed for comparison between groups. Kaplan-Meier method was performed for survival analysis and Cox proportional risk regression model was performed for multivariate analysis.@*RESULTS@#76 patients met the inclusion criteria in this study. The incidences of EGFR classical mutations 19del, 21L858R and non-classical mutations were 46.0%, 38.2% and 15.8%, respectively among these patients. There was no significant difference between the three mutations in terms of gender, age, presence of dyspnea at presentation, whether other distant metastases were combined, site of pleural effusion, volume of pleural effusion, presence of other combined effusions, tumor-node-metastasis (TNM) stage, presence of other gene mutations, and treatment of pleural effusion (P>0.05). In patients with EGFR classical mutations 19del or 21L858R or non-classical mutations subtype, the proportion of chemotherapy in first-line regimens were 17.1%, 20.7% and 58.3%, respectively (P=0.001); and first-line disease control rates were 94.3%, 75.9% and 50%, respectively (P=0.003); pleural effusion control rates were 94.3%, 79.3% and 66.7%, respectively (P=0.04); PFS were 287 d, 327 d and 55 d, respectively (P=0.001). Univariate analysis showed that EGFR mutation subtype, control of pleural effusion, first-line treatment agents, and first-line treatment efficacy were significantly associated with PFS (P<0.05). Cox multifactorial analysis showed that only EGFR mutation subtype and first-line treatment efficacy were independent prognostic factors for PFS (P<0.05).@*CONCLUSIONS@#PFS was significantly better for classical mutations than for non-classical mutations in patients with EGFR mutated lung adenocarcinoma combined with pleural effusion at initial diagnosis. Improving the efficacy of first-line therapy is the key to improve the prognosis of these patients.


Subject(s)
Adenocarcinoma of Lung/genetics , ErbB Receptors/genetics , Humans , Lung Neoplasms/pathology , Mutation , Pleural Effusion/complications , Prognosis , Retrospective Studies
9.
Chinese Journal of Lung Cancer ; (12): 147-155, 2022.
Article in Chinese | WPRIM | ID: wpr-928792

ABSTRACT

BACKGROUND@#At present, the research progress of targeted therapy for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene mutations in lung adenocarcinoma is very rapid, which brings new hope for the treatment of advanced lung adenocarcinoma patients. However, the specific imaging and pathological features of EGFR and ALK gene mutations in adenocarcinoma are still controversial. This study will further explore the correlation between EGFR, ALK gene mutations and imaging and pathological features in invasive lung adenocarcinoma.@*METHODS@#A total of 525 patients with lung adenocarcinoma who underwent surgery in our center from January 2018 to December 2019 were included. According to the results of postoperative gene detection, the patients were divided into EGFR gene mutation group, ALK gene mutation group and wild group, and the EGFR gene mutation group was divided into exon 19 and exon 21 subtypes. The pathological features of the mutation group and wild group, such as histological subtype, lymph node metastasis, visceral pleural invasion (VPI) and imaging features such as tumor diameter, consolidation tumor ratio (CTR), lobulation sign, spiculation sign, pleural retraction sign, air bronchus sign and vacuole sign were analyzed by univariate analysis and multivariate Logistic regression analysis to explore whether the gene mutation group had specific manifestations.@*RESULTS@#EGFR gene mutation group was common in women (OR=2.041, P=0.001), with more pleural traction sign (OR=1.506, P=0.042), and had little correlation with lymph node metastasis and VPI (P>0.05). Among them, exon 21 subtype was more common in older (OR=1.022, P=0.036), women (OR=2.010, P=0.007), and was associated with larger tumor diameter (OR=1.360, P=0.039) and pleural traction sign (OR=1.754, P=0.029). Exon 19 subtype was common in women (OR=2.230, P=0.009), with a high proportion of solid components (OR=1.589, P=0.047) and more lobulation sign (OR=2.762, P=0.026). ALK gene mutations were likely to occur in younger patients (OR=2.950, P=0.045), with somking history (OR=1.070, P=0.002), and there were more micropapillary components (OR=4.184, P=0.019) and VPI (OR=2.986, P=0.034) in pathology.@*CONCLUSIONS@#The EGFR and ALK genes mutated adenocarcinomas have specific imaging and clinicopathological features, and the mutations in exon 19 or exon 21 subtype have different imaging features, which is of great significance in guiding the clinical diagnosis and treatment of pulmonary nodules.


Subject(s)
Adenocarcinoma of Lung/genetics , Aged , Anaplastic Lymphoma Kinase/genetics , ErbB Receptors/genetics , Female , Genes, erbB-1 , Humans , Lung Neoplasms/pathology , Mutation , Tomography, X-Ray Computed/methods
10.
Chinese Journal of Lung Cancer ; (12): 124-129, 2022.
Article in Chinese | WPRIM | ID: wpr-928789

ABSTRACT

The incidence and mortality of lung cancer rank first among all malignant tumors in China. With the popularization of high resolution computed tomography (CT) in clinic, chest CT has become an important means of clinical screening for early lung cancer and reducing the mortality of lung cancer. Imaging findings of early lung adenocarcinoma often show partial solid nodules with ground glass components. With the development of imaging, the relationship between the imaging features of some solid nodules and their prognosis has attracted more and more attention. At the same time, with the development of 3D-reconstruction technology, clinicians can improve the accuracy of diagnosis and treatment of such nodules.This article focuses on the traditional imaging analysis of partial solid nodules and the imaging analysis based on 3D reconstruction, and systematically expounds the advantages and disadvantages of both.
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Subject(s)
Adenocarcinoma of Lung/pathology , Humans , Image Processing, Computer-Assisted , Lung Neoplasms/pathology , Solitary Pulmonary Nodule/pathology , Tomography, X-Ray Computed
11.
Article in English | WPRIM | ID: wpr-928248

ABSTRACT

Objective Many studies have revealed the crucial roles of miRNA in multiple human cancers, including lung adenocarcinoma (LUAD). In this study, we sought to explore new miRNA-mRNA pairs that are associated with LUAD prognosis. Methods A novel miRNA-mRNA regulatory network associated with prognosis in LUAD was identified and validated using the bioinformatic tools including OncomiR database, StarBase, miRnet, GEPIA2, UALCAN. Results Twenty key miRNAs were compiled after the analysis of the expression and prognostic value in OncomiR and StarBase. Targeted mRNAs of these key miRNAs were predicted in miRnet, and the resulting mRNAs were also analyzed for their prognostic values and expression patterns in GEPIA2 and UALCAN, respectively. Further expression correlation analysis was performed in StarBase. Subsequently, a new miRNA-mRNA network was built, of which each RNA pair showed negative expression correlation, opposite expression pattern, and prognostic value. Protein-protein interaction network was under construction for the mRNAs, and 19 hub genes were determined. Enrichment analysis showed that "Cell Cycle, Mitotic" was the most significantly enriched term. Then, a miRNA-hub gene sub-network was built. We selected and validated the regulatory relationship of some miRNA-hub pairs, including hsa-miR-1976/RFC2, hsa-let-7c-5p/RFC2, hsa-let-7c-5p/ESPL1, hsa-let-7c-5p/CDC25A, and hsa-miR-101-3p/KIF2C. Moreover, over-expression of hsa-miR-1976 and hsa-let-7c-5p resulted in significant cell cycle arrest. Conclusions Our results determined new prognosis-associated miRNA-mRNA pairs and might shed further light on the mechanism via which miRNA-mRNA network influences prognosis in LUAD.


Subject(s)
Adenocarcinoma of Lung/genetics , Humans , Lung Neoplasms/pathology , MicroRNAs/metabolism , Prognosis , RNA, Messenger/metabolism
12.
Article in Chinese | WPRIM | ID: wpr-927900

ABSTRACT

Objective: To investigate the mechanism that hypoxia promotes the migration of lung adenocarcinoma A549 cells. Methods: A549 cells were cultured and cells that knockdown of acetyl-CoA carboxylase 1 (ACC1) were obtained by transfection with lentivirus, and cells that knockdown of sterol regulatory element-binding proteins-1 (SREBP-1) were obtained by treated with si-RNA. A549 cells were treated with hypoxia combined with hypoxia inducible factor-1α (HIF-1α) inhibitor PX-478 (25 μmol); Hypoxia combined with linoleic acid (LA) (20 μmol) treated A549 cells with ACC1 knockdown, and A549 cells with SREBP-1 knockdown were treated by hypoxia. Transwell migration assay was used to detect cell migration. Western blot was conducted to detect HIF-1α, ACC1 and epithelial mesenchymal transition (EMT) related proteins, Vimentin, E-Cadherin and SREBP-1; Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was performed to detect the changes of ACC1 and SREBP-1 mRNA in A549 cells after hypoxia and HIF-1α inhibitor PX-478 (25 μmol) treatment. Each experiment was repeated three times. Results: Compared with the normoxic control group, hypoxia promoted the migration of A549 cells (P<0.01), and up-regulated the expressions of ACC1, HIF-1α (all P<0.01) and SREBP-1 (P<0.05). PX-478 (25 μmol) inhibited the migration of A549 cells induced by hypoxia and down-regulated the expression of SREBP-1 (all P<0.05). ACC1 mRNA and SREBP-1 mRNA levels were increased after hypoxia treatment of A549 cells (all P<0.05). The levels of ACC1 mRNA and SREBP-1 mRNA were decreased after A549 cells treated with hypoxia combined with PX-478 (25 μmol) for 24 h (P<0.05, P<0.01). Knockdown of SREBP-1 in A549 cells was obtained by transfection with si-RNA. Transwell migration assay showed the number of cell migration in si-SREBP-1 group was less than that in normoxia control group (P<0.01). The si-SREBP-1 group and the si-NC group were treated with hypoxia. Compared with the control group, the number of cell migration in the si-SREBP-1 group was decreased (P<0.01), however, the difference was not statistically significant compared with the normoxia si-SREBP-1 group (P>0.05). Western blot showed that the expression of ACC1 in the si-SREBP-1 group was lower than that in the control group (P<0.01). Compared with the control group, the expression of ACC1 was decreased after si-SREBP-1 group treated with hypoxia (P<0.01). Knockdown of ACC1 inhibited the migration of A549 cells (P<0.05). After knockdown of ACC1, the migration number of A549 cells under normoxia and 5% O2 conditions had no significant difference (P>0.05). Application of LA under hypoxia condition rescued ACC1-knockdown induced inhibitory effect on hypoxia-promoted A549 cell migration (P<0.05). Conclusion: Hypoxia promotes migration of lung adenocarcinoma A549 cells by regulating fatty acid metabolism through HIF-1α/SREBP-1/ACC1 pathway.


Subject(s)
A549 Cells , Acetyl-CoA Carboxylase , Adenocarcinoma of Lung , Cell Hypoxia/physiology , Cell Line, Tumor , Humans , Hypoxia , Hypoxia-Inducible Factor 1, alpha Subunit , Lung Neoplasms , RNA/metabolism , RNA, Messenger/metabolism , Sterol Regulatory Element Binding Protein 1/metabolism
13.
Article in Chinese | WPRIM | ID: wpr-922155

ABSTRACT

The concept of spread through air spaces (STAS) was first proposed in the World Health Organization (WHO) Classification of Tumors of the Lung, Pleura, Thymus and Heart (version 2015). STAS is defined as the micropapillary clusters, solid nests or single cells of tumor that exist in the air spaces of the surrounding lung parenchyma beyond the edge of the main tumor. Meanwhile, apart from the traditional invasion modes of lung adenocarcinoma (interstitial, visceral pleura and lym-phovascular invasion), STAS has been identified as the fourth invasion mode of lung adenocarcinoma. In recent years, the research on STAS has been a hot spot in the field of lung adenocarcinoma. The existence of STAS is related to lung cancer histopathology, gene mutation and other factors, and many studies have also confirmed that it can be used as an independent factor for tumor recurrence and prognosis. However, according to some studies, human factors can cause morphological artifacts of STAS, which still needs to be distinguished in clinical work. This paper reviews the research progress of STAS classification, related pathological features, genetic status changes, and human factors that may cause STAS artifacts.
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Subject(s)
Adenocarcinoma of Lung/pathology , Humans , Lung Neoplasms/pathology , Neoplasm Invasiveness , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Retrospective Studies
14.
Article in Chinese | WPRIM | ID: wpr-936161

ABSTRACT

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.


Subject(s)
Adenocarcinoma of Lung/drug therapy , Adrenocorticotropic Hormone/therapeutic use , Aged , B7-H1 Antigen/therapeutic use , Humans , Hydrocortisone/therapeutic use , Hyponatremia/drug therapy , Hypopituitarism/drug therapy , Immune Checkpoint Inhibitors , Lung Neoplasms/pathology , Male , Methylprednisolone/therapeutic use , Middle Aged , Nausea/drug therapy , Pituitary Gland/pathology , Pneumonia , Prednisone/therapeutic use , Programmed Cell Death 1 Receptor/therapeutic use , Prolactin/therapeutic use
15.
Article in English | WPRIM | ID: wpr-928998

ABSTRACT

The clinical data for a patient with primary lung adenocarcinoma complicated with pulmonary hamartoma, who admitted to Zunyi Medical University Hospital in September 2020, was retrospectively analyzed. The 62-years-old male visited outpatient service because of dysphagia in March 2015, and the pulmonary nodules were found. In September 2020, the computed tomography indicated the enlarged nodule in the lower lobe of left lung with lobulation, and there was ground glass nodule in the upper lobe of left lung. After thoracoscopic wedge surgery, the primary pulmonary adenocarcinoma in the upper lobe of left lung and pulmonary hamartoma in the lower lobe of left lung were confirmed by pathology. Whole exon sequencing revealed that kinesin family member 20B (KIF20B) gene was not expressed in lung adenocarcinoma, but was expressed in pulmonary hamartoma. The clinical manifestations of lung adenocarcinoma complicated with pulmonary hamartoma was not typical, which could locate in the same side and different sides of the lung. The imaging manifestations of the 2 kinds of tumors were diverse and can not be completely distinguished. The pathological examination after surgery is the gold standard, and the possibility of malignant transformation of pulmonary hamartoma should be warned.


Subject(s)
Adenocarcinoma of Lung/complications , Hamartoma/surgery , Humans , Kinesins , Lung/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Retrospective Studies
16.
Article in English | WPRIM | ID: wpr-928941

ABSTRACT

OBJECTIVE@#To study the mechanism of Chinese herbal medicine Fuzheng Kang'ai Formula (, FZKA) on tumor microenvironment (TME).@*METHODS@#CIBERSORTx was used for analysis of TME. Traditional Chinese Medicine Systems Pharmacology and Analysis Platform was applied to identify compounds-targets network and the Cancer Genome Atlas (TCGA) was employed to identify the differential expression genes (DEGs) between tumor and paracancerous tissues in lung adenocarcinoma (LUAD) from TCGA-LUAD. Additionally, DEGs with prognosis in LUAD was calculated by univariable and multivariate Cox regression. The core targets of FZKA were analyzed in lung adenocarcinoma TME. Protein-protein interaction database was employed to predict down-stream of target. Quantitative reverse transcription polymerase chain reaction was employed for biological experiment in A549, H1299 and PC9 cell lines.@*RESULTS@#The active and resting mast cells were significantly associated with prognosis of LUAD (P<0.05). Of the targets, CCNA2 as an important target of FZKA (hazard ratio=1.41, 95% confidential interval: 1.01-2.01, P<0.05) was a prognostic target and significantly associated with mast cells. CCNA2 was positively correlated with mast cell activation and negatively correlated with mast cell resting state. BCL1L2, ACTL6A and ITGAV were down-stream of CCNA2, which were validated by qRT-PCR in A549 cell.@*CONCLUSION@#FZKA could directly bind to CCNA2 and inhibit tumor growth by regulating CCNA2 downstream genes and TME of NSCLC closely related to CCNA2.


Subject(s)
Actins , Adenocarcinoma of Lung/pathology , Carcinoma, Non-Small-Cell Lung/metabolism , Chromosomal Proteins, Non-Histone , DNA-Binding Proteins , Drugs, Chinese Herbal/therapeutic use , Humans , Lung Neoplasms/metabolism , Tumor Microenvironment
18.
Arq. bras. med. vet. zootec. (Online) ; 73(5): 1111-1116, Sept.-Oct. 2021. tab, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1345263

ABSTRACT

Pulmonary adenocarcinoma is a malignant epithelial neoplasia that usually arises from conducting airways or alveolar parenchyma. It has rarely been described in wild felids, with no previous reports in ocelots. In domestic cats it is a very aggressive neoplasm with a high metastatic rate that usually evolves to death. This report aimed to describe a pulmonary adenocarcinoma in a captive and senile ocelot (Leopardus pardalis), with a thorough morphologic and immunophenotypically characterization, evidencing the epithelial-mesenchymal transition (EMT) phenomenon in a high metastatic carcinoma, an important feature rarely described in veterinary medicine, even in domestic cats.(AU)


O adenocarcinoma pulmonar é uma neoplasia epitelial maligna originada do epitélio respiratório das vias aéreas inferiores e do parênquima alveolar. É uma neoplasia raramente descrita em felinos selvagens, sem nenhum relato em jaguatiricas. Em gatos domésticos, é uma neoplasia muito agressiva, com alta taxa de metástase, e geralmente evolui para o óbito do paciente. O presente relato objetiva descrever um adenocarcinoma pulmonar em uma jaguatirica (Leopardus pardalis) senil de cativeiro, com detalhada caracterização morfológica e imunofenotípica, evidenciando o fenômeno de transição epitelial-mesenquial (TEM) em um carcinoma altamente metastático, uma característica importante, com escassos relatos na medicina veterinária, mesmo em gatos domésticos.(AU)


Subject(s)
Felidae , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/veterinary , Lung Neoplasms , Epithelial-Mesenchymal Transition , Animals, Zoo
19.
Clinics ; 76: e3222, 2021. tab, graf
Article in English | LILACS | ID: biblio-1350627

ABSTRACT

The current study found that high Zeste White 10 interactor (ZWINT) expression is related to the poor prognosis of patients with a variety of cancers. This study mainly explored the relationship between the expression level of ZWINT and the prognosis of patients with lung adenocarcinoma (LUAD). Briefly, four English databases and two high-throughput sequencing databases were searched and relevant data for meta-analysis were extracted. Pooled mean difference and 95% confidence interval (CI) were used to assess the relationships between clinical features and the expression of ZWINT. Pooled hazard ratio and 95% CI were also used to assess the relationships between clinical features and the expression level of ZWINT. This meta-analysis was registered in PROSPERO (CRD42021249475). A total of 16 high-quality datasets comprising 2,847 LUAD patients were included in this study. Higher ZWINT expression levels were found in patients younger than 65 years, males, and smokers, and were correlated with advanced TNM stages and poor prognosis. Notably, there was no publication bias in this meta-analysis. Overall, our findings indicate that ZWINT is a potential biomarker for poor prognosis and clinicopathological outcomes of patients with LUAD.


Subject(s)
Humans , Male , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Prognosis , Nuclear Proteins , Biomarkers, Tumor/analysis , Proportional Hazards Models , Intracellular Signaling Peptides and Proteins
20.
Braz. j. med. biol. res ; 54(5): e9700, 2021. tab, graf
Article in English | LILACS | ID: biblio-1180737

ABSTRACT

Lung adenocarcinomas are usually sensitive to radiation therapy, but some develop resistance. Radiation resistance can lead to poor patient prognosis. Studies have shown that lung adenocarcinoma cells (H1299 cells) can develop radioresistance through epithelial-mesenchymal transition (EMT), and this process is regulated by miRNAs. However, it is unclear which miRNAs are involved in the process of EMT. In our present study, we found that miR-183 expression was increased in a radioresistant lung adenocarcinoma cell line (H1299R cells). We then explored the regulatory mechanism of miR-183 and found that it may be involved in the regulation of zinc finger E-box-binding homeobox 1 (ZEB1) expression and mediate EMT in lung adenocarcinoma cells. qPCR results showed that miR-183, ZEB1, and vimentin were highly expressed in H1299R cells, whereas no difference was observed in E-cadherin expression. Western blot results showed that ZEB1 and vimentin were highly expressed in H1299R cells, while E-cadherin expression was decreased. When miR-183 expression was inhibited in H1299R cells, radiation resistance, proliferation, and cell migration were decreased. The expression of ZEB1 and vimentin in H1299R cells was decreased, while the expression of E-cadherin was increased. Moreover, miR-183 overexpression in H1299 cells enhanced radiation resistance, proliferative capacity, and cell migration ability. The expression of ZEB1 and vimentin in H1299 cells was increased, while that of E-cadherin was decreased. In conclusion, miR-183 may promote EMT and radioresistance in H1299 cells, and targeting the miR-183-ZEB1 signaling pathway may be a promising approach for lung cancer treatment.


Subject(s)
Humans , MicroRNAs/genetics , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/radiotherapy , Lung Neoplasms/genetics , Lung Neoplasms/radiotherapy , Gene Expression Regulation, Neoplastic , Cell Movement , Cell Line, Tumor , Epithelial-Mesenchymal Transition
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