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1.
J Cancer Educ ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38622328

ABSTRACT

Residents are actively involved in patient assessment and all aspects of patient care, and they are critical in providing nutritional support education and treatment for patients with cancer. This study aims to assess the nutritional knowledge and performance of resident physicians, providing insights into existing gaps in awareness and practices related to cancer nutrition. A total of 300 resident physicians undergoing standardized residency training in China participated in this study. An anonymous online questionnaire covering demographic characteristics, nutritional knowledge, clinical practice, and training requirements was designed and administered through the "Wenjuanxing" platform. Data were collected from June 1, 2023, to July 31, 2023. Among the participants, only 40.00% demonstrated adequate knowledge of cancer nutrition, and merely 32.00% exhibited proficient performance in nutritional care. Socio-demographic analysis revealed that residents without affiliations and those specializing in obstetrics and gynecology had superior knowledge, while surgery specialists showed significantly worse performance. Most participants expressed a lack of exposure to cancer nutrition education during academic and standardized residency training. The study highlights the demand for enhanced education and the preference for case-based teaching methods. The findings underscore an urgent need for comprehensive oncology nutrition education within China's standardized residency training. Targeted interventions and curriculum enhancements are essential to improve medical talent development and enhance patient care outcomes in oncology. The study emphasizes the critical role of practical, case-based teaching methods in addressing identified gaps in nutritional knowledge and practices among resident physicians.

2.
Diagnostics (Basel) ; 14(7)2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38611678

ABSTRACT

Bone metastasis has been reported in up to 70% of patients with advanced breast cancer. A total of 55.76% of skeletal metastases in women were derived from breast cancer. However, patients with bone metastasis from an occult primary breast cancer are a rare subset of patients. Here, we present the case of a 38-year-old woman who had sternum pain for 4 months. A whole-body PET-CT scan revealed that the FDG uptake of both the sternum and internal mammary node was significantly increased. The final diagnosis of occult breast cancer was established by immunohistochemical (IHC) staining, which is of great significance for identifying the origin of a metastatic tumor despite no visualized lesions of mammary glands.

3.
J Clin Oncol ; 42(15): 1754-1765, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38560819

ABSTRACT

PURPOSE: To identify subgroups of patients with early-stage (pT1-2N0M0) oral tongue squamous cell carcinoma (OTSCC) who may benefit from postoperative radiotherapy (PORT). PATIENTS AND METHODS: This retrospective cohort study included 528 patients diagnosed between October 2009 and December 2021. Clinicopathological characteristics and treatments with or without PORT were analyzed for their impact on outcomes. RESULTS: Among 528 patients who underwent radical surgery (median age, 62 years [IQR, 52-69]), 145 (27.5%) also underwent PORT. Multivariate analyses revealed that PORT was associated with improved survival outcomes, whereas moderate-to-poor differentiation, perineural infiltration (PNI), lymphovascular invasion (LVI), and increasing depth of invasion (DOI) were associated with poorer survival outcomes. For patients with moderate-to-poor differentiation, the surgery + PORT group showed improved outcomes compared with the surgery-alone group. After propensity score matching, the results were as follows: overall survival (OS), 97% versus 69%, P = .003; disease-free survival (DFS), 88% versus 50%, P = .001. After excluding cases with PNI/LVI, the differences persisted: OS, 97% versus 82%, P = .040; DFS, 87% versus 64%, P = .012. Similar survival benefits were observed in 104 patients with PNI and/or LVI (OS, 81% v 58%; P = .022; DFS, 76% v 47%; P = .002). In subgroups with DOI >5 mm or close margins, PORT contributed to improved DFS (80% v 64%; P = .006; 92% v 66%; P = .049) but did not significantly affect OS. CONCLUSION: Patients with moderately-to-poorly differentiated pT1-2N0M0 OTSCC benefited from PORT. Our study provided evidence that patients with PNI and/or LVI who underwent PORT had improved survival. PORT also offered DFS benefit among patients with DOI >5 mm.


Subject(s)
Neoplasm Staging , Tongue Neoplasms , Humans , Middle Aged , Male , Female , Tongue Neoplasms/pathology , Tongue Neoplasms/radiotherapy , Tongue Neoplasms/surgery , Tongue Neoplasms/mortality , Aged , Retrospective Studies , Prognosis , Radiotherapy, Adjuvant , Squamous Cell Carcinoma of Head and Neck/surgery , Squamous Cell Carcinoma of Head and Neck/pathology , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Carcinoma, Squamous Cell/surgery , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/radiotherapy
5.
Dig Dis Sci ; 69(1): 123-134, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37917212

ABSTRACT

BACKGROUND: Bile acids (BAs) are closely related to the occurrence and development of colorectal cancer (CRC), but the specific mechanism is still unclear. AIMS: To identify potential targets related to BAs in CRC and analyze the correlation with immunity. METHODS: The expression of BAs and CRC-related genes in TCGA was studied and screened using KEGG. GSE71187 was used for external validation of differentially expressed genes. Immunofluorescence, immunohistochemistry, and enzymatic cycling assays were used to detect the expression levels of the differentially expressed genes ki67 and BAs. Weighted gene coexpression network analysis (WGCNA) was used to identify genes associated with differential gene expression and immunity. The Cibersort algorithm was used to detect the infiltration of 22 kinds of immune cells in cancer tissues. The PPI network and ceRNA network were constructed to reveal the possible molecular mechanisms behind tumorigenesis. RESULTS: The BA-related gene UGT2A3 is positively correlated with good prognoses in CRC. The expression level of UGT2A3 was negatively related to the BA level and positively related to the Ki67 proliferation index. The expression level of UGT2A3 was higher in the moderately differentiation and advanced stage (stage IV) of CRC. In addition, the expression level of UGT2A3 is correlated with CD8+ T cells. A PPI network related to UGT2A3 and T-cell immune-related genes was constructed. A ceRNA network containing 32 miRNA‒mRNA and 40 miRNA‒lncRNA regulatory pairs was constructed. CONCLUSION: UGT2A3 is a potential molecular target of bile acids in the regulation of CRC and is related to T-cell immunity.


Subject(s)
Colorectal Neoplasms , MicroRNAs , Humans , Bile Acids and Salts , Ki-67 Antigen , Algorithms , Colorectal Neoplasms/genetics
6.
Cancers (Basel) ; 15(21)2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37958309

ABSTRACT

The objective of this study was to evaluate the discriminative capabilities of radiomics signatures derived from three distinct machine learning algorithms and to identify a robust radiomics signature capable of predicting pathological complete response (pCR) after neoadjuvant chemoradiotherapy in patients diagnosed with locally advanced rectal cancer (LARC). In a retrospective study, 211 LARC patients were consecutively enrolled and divided into a training cohort (n = 148) and a validation cohort (n = 63). From pretreatment contrast-enhanced planning CT images, a total of 851 radiomics features were extracted. Feature selection and radiomics score (Radscore) construction were performed using three different machine learning methods: least absolute shrinkage and selection operator (LASSO), random forest (RF) and support vector machine (SVM). The SVM-derived Radscore demonstrated a strong correlation with the pCR status, yielding area under the receiver operating characteristic curves (AUCs) of 0.880 and 0.830 in the training and validation cohorts, respectively, outperforming the RF and LASSO methods. Based on this, a nomogram was developed by combining the SVM-based Radscore with clinical indicators to predict pCR after neoadjuvant chemoradiotherapy. The nomogram exhibited superior predictive power, achieving AUCs of 0.910 and 0.866 in the training and validation cohorts, respectively. Calibration curves and decision curve analyses confirmed its appropriateness. The SVM-based Radscore demonstrated promising performance in predicting pCR for LARC patients. The machine learning-driven nomogram, which integrates the Radscore and clinical indicators, represents a valuable tool for predicting pCR in LARC patients.

7.
J Neurooncol ; 165(1): 127-137, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37848757

ABSTRACT

PURPOSE: To investigate the impact of radiotherapy (RT) and immune checkpoint inhibitor (ICI) sequence on the survival outcome in NSCLC patients with brain metastasis, and decide the best time to initiate RT. METHODS: Patients were managed with delayed RT (ICI delivered over 2 weeks prior to RT), concurrent RT (ICI delivered within 2 weeks prior to or after RT), or upfront RT (RT delivered over 2 weeks prior to ICI). Overall survival (OS), intracranial local progression-free survival (iLPFS), and intracranial distant progression-free survival (iDPFS) were assessed. A meta-analysis was performed to analyze the association between survival outcome and RT/ICI sequence. RESULTS: A total of 73 NSCLC patients were identified with a median follow-up of 13.9 months. Patients who receive delayed RT demonstrated shorter iLPFS (P = 0.0029), iDPFS (P = 0.016), and OS (P < 0.001). A meta-analysis was conducted and a total of 4 studies, 254 patients were included. The HR was 0.44 for iDPFS (P = 0.03), 0.41 for OS (P < 0.01) when compared concurrent with delayed RT, 0.21 for iDPFS (P < 0.01), 0.32 for OS (P < 0.01) when compared upfront with delayed RT, consistent with our conclusion that delayed RT brought with worst iDPFS and OS. More importantly, the best overall response rate (BOR) decreased in cases with longer RT and ICI intervals. Patients who receive intervals of RT and ICI within 7 days achieve the best median BOR of - 53%. CONCLUSIONS: Delayed RT brought poor survival outcomes including iLPFS, iDPFS, and OS in NSCLC patients. The shorter interval of RT and ICI is associated with better BOR.


Subject(s)
Brain Neoplasms , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Immune Checkpoint Inhibitors , Carcinoma, Non-Small-Cell Lung/radiotherapy , Programmed Cell Death 1 Receptor , Lung Neoplasms/therapy , Brain Neoplasms/drug therapy , Brain Neoplasms/radiotherapy , Retrospective Studies
8.
Front Mol Biosci ; 10: 1162409, 2023.
Article in English | MEDLINE | ID: mdl-37503539

ABSTRACT

Objectives: The goal of our bioinformatics study was to comprehensively analyze the association between the whole calpain family members and the progression and prognosis of hepatocellular carcinoma (HCC). Methods: The data were collected from The Cancer Genome Atlas (TCGA). The landscape of the gene expression, copy number variation (CNV), mutation, and DNA methylation of calpain members were analyzed. Clustering analysis was performed to stratify the calpain-related groups. The least absolute shrinkage and selection operator (LASSO)-based Cox model was used to select hub survival genes. Results: We found 14 out of 16 calpain members expressed differently between tumor and normal tissues of HCC. The clustering analyses revealed high- and low-risk calpain groups which had prognostic difference. We found the high-risk calpain group had higher B cell infiltration and higher expression of immune checkpoint genes HAVCR2, PDCD1, and TIGHT. The CMap analysis found that the histone deacetylase (HDAC) inhibitor trichostatin A and the PI3K-AKT-mTOR pathway inhibitors LY-294002 and wortmannin might have a therapeutic effect on the high-risk calpain group. The DEGs between calpain groups were identified. Subsequent univariate Cox analysis of each DEG and LASSO-based Cox model obtained a calpain-related prognostic signature. The risk score model of this signature showed good ability to predict the overall survival of HCC patients in TCGA datasets and external validation datasets from the Gene Expression Omnibus database and the International Cancer Genome Consortium database. Conclusion: We found that calpain family members were associated with the progression, prognosis, and drug response of HCC. Our results require further studies to confirm.

9.
J Med Microbiol ; 72(6)2023 Jun.
Article in English | MEDLINE | ID: mdl-37294282

ABSTRACT

Introduction. Differences in gut bacteria that are associated with the occurrence and development of colorectal cancer (CRC) exist between sexes, and males have a higher morbidity of CRC.Gap Statement. Clinical data for the relationship between gut bacteria and sexes in patients with CRC are not available and are needed to support individualized screening and treatment programmes.Aim. To analyse the relationship between gut bacteria and sexes in patients with CRC.Methodology. A total of 6 077 samples recruited by Fudan University's Academy of Brain Artificial Intelligence Science and Technology were included, and the gut bacteria composition mainly shows the top 30 genera. Linear discriminant analysis Effect Size (LEfSe) was used to analyse the differences in gut bacteria. Pearson correlation coefficients were calculated to demonstrate the relationship of discrepant bacteria. CRC risk prediction models were used to rank the importance of valid discrepant bacteria.Results. Bacteroides, Eubacterium and Faecalibacterium were the top three bacteria in males with CRC, while Bacteroides, Subdoligranulum and Eubacterium were the top three bacteria in females with CRC. The abundance of gut bacteria (Escherichia, Eubacteriales, Clostridia, etc.) was higher in males with CRC compared with that in females with CRC. In addition, Dorea and Bacteroides were important CRC-related bacteria (P<0.001). Finally, the importance of discrepant bacteria was ranked based on CRC risk prediction models. Blautia, Barnesiella and Anaerostipes were the top three important discrepant bacteria between males with CRC and females with CRC. The value of AUC was 1.0, the sensitivity was 92.0 %, the specificity was 68.4 %, and the accuracy was 83.3 % in the discovery set.Conclusion. Gut bacteria were correlated with sexes and CRC. It is necessary to consider gender when gut bacteria are used to treat and predict CRC.


Subject(s)
Colorectal Neoplasms , Gastrointestinal Microbiome , Humans , Male , Female , Colorectal Neoplasms/microbiology , Sex Characteristics , Artificial Intelligence , Feces/microbiology , Bacteria/genetics
10.
Signal Transduct Target Ther ; 8(1): 205, 2023 05 19.
Article in English | MEDLINE | ID: mdl-37208386

ABSTRACT

As one of the four major means of cancer treatment including surgery, radiotherapy (RT), chemotherapy, immunotherapy, RT can be applied to various cancers as both a radical cancer treatment and an adjuvant treatment before or after surgery. Although RT is an important modality for cancer treatment, the consequential changes caused by RT in the tumor microenvironment (TME) have not yet been fully elucidated. RT-induced damage to cancer cells leads to different outcomes, such as survival, senescence, or death. During RT, alterations in signaling pathways result in changes in the local immune microenvironment. However, some immune cells are immunosuppressive or transform into immunosuppressive phenotypes under specific conditions, leading to the development of radioresistance. Patients who are radioresistant respond poorly to RT and may experience cancer progression. Given that the emergence of radioresistance is inevitable, new radiosensitization treatments are urgently needed. In this review, we discuss the changes in irradiated cancer cells and immune cells in the TME under different RT regimens and describe existing and potential molecules that could be targeted to improve the therapeutic effects of RT. Overall, this review highlights the possibilities of synergistic therapy by building on existing research.


Subject(s)
Neoplasms, Radiation-Induced , Tumor Microenvironment , Humans , Immunotherapy , Combined Modality Therapy
11.
Int J Biol Macromol ; 242(Pt 4): 125037, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37245768

ABSTRACT

Introduction of the sulfonic acid group into H-ß zeolite to prepare ß-SO3H bifunctional catalysts for the efficient synthesis of 5-hydroxymethylfurfural (HMF) from cellulose. Catalysts characterization, such as XRD, ICP-OES, SEM (Mapping), FTIR, XPS, N2 adsorption-desorption isotherm, NH3-TPD, Py-FTIR demonstrate the sulfonic acid group was successfully grafted onto the ß zeolite. A superior HMF yield (59.4 %) and cellulose conversion (89.4 %) was obtained in the H2O(NaCl)/THF biphasic system under 200 °C for 3 h with ß-SO3H(3) zeolite as catalyst. More valuable, ß-SO3H(3) zeolite converts other sugars and obtains ideal HMF yield, including fructose (95.5 %), glucose (86.5 %), sucrose (76.8 %), maltose (71.5 %), cellobiose (67.0 %), starch (68.1 %), glucan (64.4 %) and also converts plant material (25.1 % for moso bamboo and 18.7 % for wheat straw) with great HMF yield. ß-SO3H(3) zeolite catalyst keeps an appreciable recyclability after 5 cycles. Moreover, in the presence of ß-SO3H(3) zeolite catalyst, the by-products during the production of HMF from cellulose were detected, and the possible conversion pathway of cellulose to HMF was proposed. The ß-SO3H bifunctional catalyst has excellent potential for the biorefinery of high value platform compound from carbohydrates.


Subject(s)
Cellulose , Zeolites , Cellulose/metabolism , Sulfonic Acids , Carbohydrates , Acids , Furaldehyde , Catalysis
12.
Front Oncol ; 13: 1093155, 2023.
Article in English | MEDLINE | ID: mdl-37077821

ABSTRACT

Objective: We aim to explore the clinicopathological features associated with axillary node response and recurrence in breast cancer patients undergoing neoadjuvant treatment (NAT). Methods: We retrospectively reviewed the medical records of 486 stage I to III breast cancer patients who received NAT and surgery between 2016 and 2021. Results: A total of 486 cases were reviewed and 154 (31.7%) patients achieved breast pathological complete response (pCR) (ypT0/Tis). Of the 366 cases with initially cN+, 177 (48.4%) cases reach ypN0. Breast pCR is in high accordance to axillary pCR (81.5%). Hormone receptor (HR)-/HER2+ breast cancer patients have the highest axillary pCR rate (78.3%). Patients achieve axillary pCR have a significantly better disease-free survival (DFS) (P=0.0004). Further analysis reveals that the DFS of ypN0 and ypN1 cases are similar (P=0.9049). Moreover, DFS in patients with ypN0 (P<0.0001) and ypN1 (P<0.0001) is significantly better than that in patients with ypN2-3. For post-mastectomy ypN0 cases, radiation could only improve DFS in patients with initially cN+ stage (P=0.0499). Multivariate Cox regression analysis shows that radiation is an independent factor to improve DFS (Hazard ratio (HR): 0.288(0.098-0.841), P=0.0230). Radiation does not improve DFS in pre-cN0/ypN0 patients (P=0.1696). Conclusion: Axillary pCR rate is higher than breast pCR rate. HR-/HER2+ patients have the highest axillary pCR rate. Axillary pCR is associated with better DFS. Radiation could further improve DFS in ypN0 patients with initially positive nodal disease.

13.
Front Oncol ; 13: 1101225, 2023.
Article in English | MEDLINE | ID: mdl-36910606

ABSTRACT

Aim: This study aimed to examine the effect of the weight initializers on the respiratory signal prediction performance using the long short-term memory (LSTM) model. Methods: Respiratory signals collected with the CyberKnife Synchrony device during 304 breathing motion traces were used in this study. The effectiveness of four weight initializers (Glorot, He, Orthogonal, and Narrow-normal) on the prediction performance of the LSTM model was investigated. The prediction performance was evaluated by the normalized root mean square error (NRMSE) between the ground truth and predicted respiratory signal. Results: Among the four initializers, the He initializer showed the best performance. The mean NRMSE with 385-ms ahead time using the He initializer was superior by 7.5%, 8.3%, and 11.3% as compared to that using the Glorot, Orthogonal, and Narrow-normal initializer, respectively. The confidence interval of NRMSE using Glorot, He, Orthogonal, and Narrow-normal initializer were [0.099, 0.175], [0.097, 0.147], [0.101, 0.176], and [0.107, 0.178], respectively. Conclusions: The experiment results in this study indicated that He could be a valuable initializer in the LSTM model for the respiratory signal prediction.

14.
Immunobiology ; 228(2): 152352, 2023 03.
Article in English | MEDLINE | ID: mdl-36827833

ABSTRACT

BACKGROUND: The mechanism of immunity in the development of colorectal cancer (CRC) has been studied in-depth, but knowledge of its role in the treatment of CRC is limited. OBJECTIVE: This study aimed to classify CRC based on immunology and construct an immune-related prognostic model. METHODS: Nine expression profile datasets of CRC, comprising 1640 samples, were downloaded from the NCBI GEO database. Immune infiltration of CRC was estimated using 5 algorithms. Based on the relative infiltration level of immune cells, immune score, and stromal score, immunosubtype analysis of tumors was conducted. Differentially expressed genes (DEGs) between the two subtypes were screened, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. Hematoxylin eosin (HE) staining, immunohistochemical (IHC) staining and qPCR were used to verify the correlation between DEGs and differentiation degree of cancer and the expression of Ki67. Subsequently, a risk signature was constructed based on the least absolute shrinkage and selection operator (LASSO) model. RESULTS: Based on the infiltration level, immune score, and stromal score of each immune cell, CRC was divided into three immune cell subtypes. Most immune checkpoint genes showed highly significant differences among the three cell subtypes, and most of the co-stimulatory and co-inhibitory molecules were lower in cluster 1 and the highest in cluster 3. Next, 50 common DEGs were determined from the intersections of the different subtypes. Among these common DEGs, 25 were identified to be relevant to the prognosis of CRC patients. The mRNA expressions of C5orf46, CYP1B1, MIR100HG, SFRP2 and CXCL13 was related to clinical prognostic indicators. Finally, these 5 DEGs were included in a prognostic risk signature model, which effectively identified high-risk groups among CRC patients in both the training and validation sets. CONCLUSION: In this study, CRCs were divided into three subtypes based on immunology, and the different subtypes led to different prognosis. Additionally, a prognostic model was constructed based on five immune-related DEGs to distinguish the three subtypes.


Subject(s)
Algorithms , Colorectal Neoplasms , Humans , Prognosis , Cell Differentiation , Eosine Yellowish-(YS)
15.
Mol Pharm ; 20(2): 1025-1038, 2023 02 06.
Article in English | MEDLINE | ID: mdl-36571795

ABSTRACT

Boron neutron capture therapy (BNCT) is becoming a promising radiation treatment technique dealing with tumors due to its cellular targeting specificity. In this article, based on the biocompatible chitosan oligosaccharide (COS), we designed a boron delivery system using carborane (CB) as a boron drug with cRGD peptide modification and paclitaxel (PTX) loaded in the hydrophobic core. The nanoparticles (cRGD-COS-CB/PTX) realized the boron delivery into tumor sites with an enhanced permeability and retention (EPR) effect and an active targeting effect achieved by the cRGD-integrin interaction on the surface of tumor cells. The uniform spherical nanoparticles can be selectively taken by hepatoma cells rather than normal hepatocytes. In vivo experiments showed that the nanoparticles had a targeting effect on tumor sites in both subcutaneous and orthotopic tumor models, which was an encouraging result for radiotherapy for liver cancer. To sum up, the nanoparticles we produced proved to be promising dual-functionalized nanoparticles for radiotherapy and chemotherapy.


Subject(s)
Boranes , Boron Neutron Capture Therapy , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/radiotherapy , Boron Neutron Capture Therapy/methods , Boron , Liver Neoplasms/drug therapy , Liver Neoplasms/radiotherapy , Oligosaccharides , Cell Line, Tumor
16.
Front Immunol ; 13: 1001506, 2022.
Article in English | MEDLINE | ID: mdl-36405741

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is the most prevalent pathological type of liver cancer worldwide with high mortality and poor prognosis. N6-methyladenosine (m6A) can modify RNAs such as mRNA, lncRNA, miRNA, and tRNA, thereby playing a critical role in the pathogenesis of HCC. However, the role of m6A-associated small nuclear RNA (snRNA) in the prognostic value and immunotherapeutic response in HCC remains unclear. Materials and methods: In this study, snRNA expression data, gene mutation data, and clinical data of HCC patients were acquired from The Cancer Genome Atlas (TCGA) database. We used the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to identify significant prognostic m6A-associated snRNAs, and then developed a multivariate Cox model based on the selected snRNAs. HCC patients were split into low- and high-risk groups based on the median risk score. We subsequently performed Kaplan-Meier curve analysis to estimate overall survival (OS) by clinicopathological characteristics and tumor mutational burden (TMB) status in low- and high-risk HCC patients. Finally, we compared the immunotherapeutic response as represented by tumor immune dysfunction and exclusion (TIDE) scores between the two risk groups. Results: Eight m6A-associated snRNAs were selected as independent predictors to develop the risk model. Our results revealed that the OS of HCC patients in the high-risk group was significantly worse than that in the low-risk group on clinicopathologic characteristics, including age (≤65 years and >65 years), gender (male), grade (G I-II and G III-IV) and TNM staging (Stage I-II and Stage III-IV). In addition, the OS of low-TMB and low-risk group was longer than that of high-TMB and high-risk group. The TIDE score indicated that HCC patients in the high-risk group were more susceptible to immunotherapy. Conclusion: Our study suggests that m6A-associated snRNAs may be useful biomarkers for the prognosis of HCC and that m6A-associated snRNA models can predict the effect of immunotherapy in HCC patients.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Male , Aged , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/therapy , Liver Neoplasms/metabolism , RNA, Small Nuclear , Prognosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Immunotherapy/adverse effects
17.
Pathol Res Pract ; 238: 154136, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36155324

ABSTRACT

DNA methylation is a crucial epigenetic modification in hepatocellular carcinoma (HCC), and hepatitis C virus (HCV) can induce hepatocarcinogenesis. Nevertheless, the interaction mechanism between DNA methylation and HCV infection in HCC is still ambiguous. In this study, we performed a comprehensive meta-analysis to assess the contribution of DNA methylation in HCV-associated HCC. After four steps of literature screening, we finally obtained 33 qualified case-control studies for this meta-analysis. These studies consisted of 587 HCV-positive cancer tissues and 326 HCV-negative cancer tissues. Our results revealed that four genes (p16, GSTP1, APC, and RUNX3) were more hypermethylated in the HCV-positive liver cancer tissues than in the HCV-negative liver cancer tissues. In addition, the p16 gene was more hypermethylated in the HCV-positive paracancerous tissues than in the HCV-negative paracancerous tissues. Subgroup meta-analysis by geographical populations showed that p16 methylation was significantly higher in HCV-positive cancerous tissues from Japanese and Chinese. Besides, p16 methylation was significantly higher among patients (> 60 years) but not among the others (≤ 60 years). However, there was no obvious association between DNA methylation and other clinicopathological characteristics, including gender, tumor size, differentiation, and clinical stage. Our study suggested that DNA methylation could become potential biomarkers for HCV-associated HCC. DNA methylation contributed to the risk of HCV-associated HCC.

18.
J Gastroenterol Hepatol ; 37(11): 2039-2050, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36066844

ABSTRACT

Hepatocellular carcinoma (HCC) is the most common liver malignancy that can be developed from hepatitis B and cirrhosis. Many pathophysiological alterations, including hepatitis B virus (HBV) DNA integration, oxidative stress, cytokine release, telomerase homeostasis, mitochondrial damage, epigenetic modification, and tumor microenvironment, are involved in the biological process from hepatitis B to cirrhosis and HCC. N6-methyladenosine (m6A), as an epitranscriptomic modification of RNAs, can regulate the stability, splicing, degradation, transcription, and translation of downstream target RNAs in HBV and liver cancer cells. m6A regulators (writers, erasers, and readers) play an important role in the pathogenesis of HBV-associated HCC by regulating cell proliferation, apoptosis, migration, autophagy, differentiation, inflammation, angiogenesis, and tumor microenvironment. This review summarizes the current progress of m6A methylation in the molecular mechanisms, biological functions, and potential clinical implications of HBV-associated HCC.


Subject(s)
Carcinoma, Hepatocellular , Hepatitis B , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Hepatitis B virus/genetics , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Methylation , Hepatitis B/complications , Liver Cirrhosis/complications , RNA/metabolism , Tumor Microenvironment/genetics
19.
Front Immunol ; 13: 968649, 2022.
Article in English | MEDLINE | ID: mdl-36059542

ABSTRACT

Fusobacterium nucleatum (F. nucleatum) is originally an oral opportunistic pathogen and accumulating evidence links the presence of F. nucleatum with the pathogenicity, development, and prognosis of colorectal cancer (CRC). However, only limited preliminary data is available dealing with the role of F. nucleatum in other malignancies except for CRC. The present review aims to update and systematize the latest information about the mechanisms of F. nucleatum-mediating carcinogenesis, together with the detection rates, clinicopathological, and molecular features in F. nucleatum-associated malignancies. Comparing with adjacent non-tumorous tissue, previous studies have shown an overabundance of intratumoural F. nucleatum. Although the prognostic role of F. nucleatum is still controversial, a higher prevalence of F. nucleatum was usually associated with a more advanced tumor stage and a worse overall survival. Preliminary evidence have shown that epithelial-to-mesenchymal transition (EMT) and relevant inflammation and immune response aroused by F. nucleatum may be the probable link between F. nucleatum infection and the initiation of oral/head and neck cancer. Further studies are needed to elucidate the etiologic role of the specific microbiota and the connection between the extent of periodontitis and carcinogenesis in different tumor types. The mechanisms of how the antibiotics exerts the critical role in the carcinogenesis and antitumor effects in malignancies other than CRC need to be further explored.


Subject(s)
Colorectal Neoplasms , Fusobacterium Infections , Carcinogenesis , Colorectal Neoplasms/pathology , Fusobacterium nucleatum , Humans , Prognosis
20.
J Leukoc Biol ; 112(6): 1669-1676, 2022 12.
Article in English | MEDLINE | ID: mdl-36000310

ABSTRACT

T lymphocytes are the key protective contributors in chronic infection and tumor, but experience exhaustion by persistent antigen stimulation. As an unconventional lineage of T cells, γδ T cells can rapidly response to varied infectious and tumor challenges in a non-MHC-restricted manner and play key roles in immune surveillance via pleiotropic effector functions, showing promising as candidates for cellular tumor immunotherapy. Activated γδ T cells can also acquire exhaustion signature with elevated expression of immune checkpoints, such as PD-1, decreased cytokine production, and functional impairment. However, the exhaustion features of γδ T cells are distinct from conventional αß T cells. Here, we review the researches regarding the characteristics, heterogeneity, and mechanisms of γδ T cell exhaustion. These studies provide insights into the combined strategies to overcome the exhaustion of γδ T cells and enhance antitumor immunity. Summary sentence: Review of the characteristics, heterogeneity, and mechanisms of γδ T cell exhaustion provides insights into the combined strategies to enhance γδ T cell-based antitumor immunotherapy.


Subject(s)
Intraepithelial Lymphocytes , Neoplasms , Humans , Receptors, Antigen, T-Cell, gamma-delta , Immunotherapy , Neoplasms/therapy
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