scholarly journals The m6A Methylation Gene SNRPC can be used as a Biomarker for the Prognosis and Immunotherapy of Hepatocellular Carcinoma

Author(s):  
Jihao Cai ◽  
Minglei Zhou ◽  
Jianxin Xu

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. Due to its complex pathogenic factors, the prognosis of HCC is poor. Therefore, a credible prognostic biomarker is urgently needed for this disease. N6-methyladenosine (m6A) RNA methylation plays an important role in the tumorigenesis, progression and prognosis of many tumors. However, studies on the prognostic and therapeutic value of this modification in HCC are lacking.Case Presentation: The HCC RNA-seq profiles in The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, including 421 LIHC and 440 LIRI samples respectively, were used in this study. The expressive distinction of 21 RNA methylation regulators between HCC and normal tissue were firstly assessed and SNRPC was obtained. Then the expression of SNRPC was validated as a risk factor for prognosis by Kaplan-Meier analysis and employed to establish a nomogram with T pathologic stage. By GSVA and GSEA analyses, we found SNRPC was mainly related to protein metabolism and immune process. Further, ESTIMATE, MCP-counter and single sample GSEA (ssGSEA) algorithm showed high-SNRPC expression group had lower stromal scores, a lower abundance of endothelial cells, fibroblasts and immune infiltration. Ultimately, Tumor Immune Dysfunction and Exclusion (TIDE) analysis exhibited high-SNRPC expression group showed non-response to immune checkpoint inhibitor therapy, especially to a PD-1 inhibitor.Conclusion: SNRPC could serve as valuable prognostic and immunotherapeutic marker in HCC. We provide here an accurate nomogram for clinical diagnosis using SNRPC as a biomarker.

2020 ◽  
Author(s):  
Qikuan He ◽  
Pengyi Guo ◽  
Yunshou Lin ◽  
Zhongjing Zhang ◽  
Yanning Lv ◽  
...  

Abstract Background: Circadian clock genes have been reported to exhibit a regulatory effect on the carcinogenesis and progression of numerous cancers. Nevertheless, the specific relationship between hepatocellular carcinoma (HCC) and circadian rhythm associated genes still remain to be clarified. Therefore, we evaluate the prognosis function of circadian clock genes in HCC with the online datasets of The Cancer Genome Atlas (TCGA) and the international cancer genome consortium (ICGC). Methods: In our research, the RNA-seq of the selected core circadian genes in HCC patients and their relevant clinical data were acquired from the online TCGA database and the ICGC database. R software and cBioPortal website were performed. Results: As consequence, among the 22 typical circadian clock genes, 16 genes were statistically expressed between HCC and adjacent normal tissues. Accordingly, 11 clock genes with regression coefficients were used to constitute a new risk score formula, which was related to the prognosis in HCC. Moreover, the new nomogram, which consisting risk score and several clinical traits , could be applied for the purpose of accurate prediction of the OS time for the patients. Finally, we identified a novel nomogram related with OS in HCC patients with a comprehensive analysis of circadian clock genes and other clinical characteristics profiles. It was also the first time we systematically demonstrated the relationship between clock genes and the HCC prognosis, which would contribute to the treatment of HCC. Conclusions: The current study demonstrated the potential of circadian clock genes as clinically associated biomarkers for prognosis prediction in HCC, which may make a significant contribution to the further investigations of HCC progression.


2021 ◽  
Author(s):  
Jun Du ◽  
Jinguo Wang

Abstract Background: The expression and molecular mechanism of cysteine rich transmembrane module containing 1 (CYSTM1) in human tumor cells remains unclear. The aim of this study was to determine whether CYSTM1 could be used as a potential prognostic biomarker for hepatocellular carcinoma (HCC).Methods: We first demonstrated the relationship between CYSTM1 expression and HCC in various public databases. Secondly, Kaplan–Meier analysis and Cox proportional hazard regression model were performed to evaluate the relationship between the expression of CYSTM1 and the survival of HCC patients which data was downloaded in the cancer genome atlas (TCGA) database. Finally, we used the expression data of CYSTM1 in TCGA database to predict CYSTM1-related signaling pathways through bioinformatics analysis.Results: The expression level of CYSTM1 in HCC tissues was significantly correlated with T stage (p = 0.039). In addition, Kaplan–Meier analysis showed that the expression of CYSTM1 was significantly associated with poor prognosis in patients with early-stage HCC (p = 0.003). Multivariate analysis indicated that CYSTM1 is a potential predictor of poor prognosis in HCC patients (p = 0.036). The results of biosynthesis analysis demonstrated that the data set of CYSTM1 high expression was mainly enriched in neurodegeneration and oxidative phosphorylation pathways.Conclusion: CYSTM1 is an effective biomarker for the prognosis of patients with early-stage HCC and may play a key role in the occurrence and progression of HCC.


2020 ◽  
Author(s):  
Gang Xu ◽  
Xiaoxiang Zhou ◽  
Jiali Xing ◽  
Yao Xiao ◽  
Bao Jin ◽  
...  

Abstract Background: RAS association domain family protein 1A (RASSF1A) promoter hypermethylation is suggested to be linked to hepatocellular carcinoma (HCC), but the results remained controversial.Methods: We evaluated how RASSF1A promoter hypermethylation affects HCC risk and its clinicopathological characteristics through meta-analysis. Data on DNA methylation in HCC and relevant clinical data were also collected based on The Cancer Genome Atlas (TCGA) database to investigate the prognostic role of RASSF1A promoter hypermethylation in HCC.Results: Forty-four articles involving 4,777 individuals were enrolled in the pooled analyses. The RASSF1A promoter methylation rate was notably higher in the HCC cases than the non-tumor cases and healthy individuals, and was significantly related to hepatitis B virus (HBV) infection-positivity and large tumor size. Kaplan–Meier survival analysis revealed that HCC cases with RASSF1A promoter hypermethylation had worse outcomes. Receiver operating characteristic curves confirmed that RASSF1A promoter methylation may be a marker of HCC-related prognoses.Conclusions: RASSF1A promoter hypermethylation is a promising biomarker for the diagnosis of HCC from tissue and peripheral blood, and is an emerging therapeutic target against HCC.


2020 ◽  
Author(s):  
Xuehui Peng ◽  
Yonggang He ◽  
Xiaobing Huang ◽  
Nan You ◽  
Huiying Gu ◽  
...  

Abstract Background: The tumorigenesis and development of hepatocellular carcinoma (HCC) is a process involving multiple factors. The COMMDs family proteins were reported to play important roles in various disease and cancers including HCC. We previously found COMMD7 acted as a HCC-promotion factor; however, further understanding on COMMD7 was needed. We conducted these bioinformatics analysis for the purpose of comprehensive understanding of the functional role of COMMD7 in HCC.Methods: The bioinformatics analysis of COMMD7 were launched by online platforms including KEGG, GEPIA, cBioportal, Gene Ontology and The Kaplan-Meier plotter. Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were downloaded, and the data analysis and processing were conducted by RStudio (version 1.3.959) software.Results: The expression profile results of COMMD7 in TCGA and GTEx database suggested that COMMD7 expressed highly in liver tumor tissues and positively related with poorer prognosis (p<0.01); COMMD7 also contributed to the early development of HCC as its higher expression resulted in progression from stage I to stage III (p<0.01). Based on our previous studies, COMMD7 may target NF-κB signaling and CXCL10 to enhance the proliferation of hepatoma cells so that promoting the development of HCC. Conclusions:This study updates the current studies about the newly recognized roles of COMMD7 in the progression of HCC, summarizing the research progress and prospects of COMMD7 comprehensively, offering an outlook for the future investigation and targeted therapy of HCC.


2011 ◽  
Vol 35 (8) ◽  
pp. 1732-1737 ◽  
Author(s):  
N. Thao T. Nguyen ◽  
Ron T. Cotton ◽  
Theresa R. Harring ◽  
Jacfranz J. Guiteau ◽  
Marie-Claude Gingras ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Wenli Li ◽  
Jun Liu ◽  
Zhanzhong Ma ◽  
Xiaofeng Zhai ◽  
Binbin Cheng ◽  
...  

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and N6-methyladenosine (m6A) is a predominant internal modification of RNA in various cancers. We obtained the expression profiles of m6A-related genes for HCC patients from the International Cancer Genome Consortium and The Cancer Genome Atlas datasets. Most of the m6A RNA methylation regulators were confirmed to be differentially expressed among groups stratified by clinical characteristics and tissues. The clinical factors (including stage, grade, and gender) were correlated with the two subgroups (cluster 1/2). We identified an m6A RNA methylation regulator-based signature (including METTL3, YTHDC2, and YTHDF2) that could effectively stratify a high-risk subset of these patients by univariate and LASSO Cox regression, and receiver operating characteristic (ROC) analysis indicated that the signature had a powerful predictive ability. Immune cell analysis revealed that the genes in the signature were correlated with B cell, CD4 T cell, CD8 T cell, dendritic cell, macrophage, and neutrophil. Functional enrichment analysis suggested that these three genes may be involved in genetic and epigenetic events with known links to HCC. Moreover, the nomogram was established based on the signature integrated with clinicopathological features. The calibration curve and the area under ROC also demonstrated the good performance of the nomogram in predicting 3- and 5-year OS in the ICGC and TCGA cohorts. In summary, we demonstrated the vital role of m6A RNA methylation regulators in the initial presentation and progression of HCC and constructed a nomogram which would predict the clinical outcome and provide a basis for individualized therapy.


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