Dataset Information

A novel DNA methylation-driver gene signature for long-term survival prediction of hepatitis-positive hepatocellular carcinoma patients.

ABSTRACT:

Background

Abnormal DNA methylation is one of the most general epigenetic modifications in hepatocellular carcinoma (HCC). Recent research showed that DNA methylation was a prognostic indicator of all-cause HCC and nonviral HCC. However, whether DNA methylation-driver genes could be used for predicting survival, the probability of hepatitis-positive HCC remains unclear.

Methods

In this study, DNA methylation-driver genes (MDGs) were screened by a joint analysis of methylome and transcriptome data of 142 hepatitis-positive HCC patients. Subsequently, a prognostic risk score and nomogram were constructed. Finally, correlation analyses between the risk score and signaling pathways and immunity were conducted by GSVA and CIBERSORT.

Results

Through random forest screening and Cox progression analysis, 10 prognostic methylation-driver genes (AC008271.1, C11orf53, CASP8, F2RL2, GBP5, LUCAT1, RP11-114B7.6, RP11-149I23.3, RP11-383 J24.1, and SLC35G2) were screened out. As a result, a prognostic risk score signature was constructed. The independent value of the risk score for prognosis prediction were addressed in the TCGA-HCC and the China-HCC cohorts. Next, clinicopathological features were analyzed and HBV status and histological grade were screened to construct a nomogram together with the risk score. The prognostic efficiency of the nomogram was validated by the calibration curves and the concordance index (C index: 0.829, 95% confidence interval: 0.794-0.864), while its clinical application ability was confirmed by decision curve analysis (DCA). At last, the relationship between the risk score and signaling pathways, as well as the correlations between immune cells were elucidated preliminary.

Conclusions

Taken together, our study explored a novel DNA methylation-driver gene risk score signature and an efficient nomogram for long-term survival prediction of hepatitis-positive HCC patients.

SUBMITTER: Fu J

PROVIDER: S-EPMC9741990 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

A novel DNA methylation-driver gene signature for long-term survival prediction of hepatitis-positive hepatocellular carcinoma patients.

Fu Jie J Qin Wei W Tong Qing Q Li Zhenghao Z Shao Yaoli Y Liu Zhiqiang Z Liu Chun C Wang Zicheng Z Xu Xundi X

Cancer medicine 20220530 23

<h4>Background</h4>Abnormal DNA methylation is one of the most general epigenetic modifications in hepatocellular carcinoma (HCC). Recent research showed that DNA methylation was a prognostic indicator of all-cause HCC and nonviral HCC. However, whether DNA methylation-driver genes could be used for predicting survival, the probability of hepatitis-positive HCC remains unclear.<h4>Methods</h4>In this study, DNA methylation-driver genes (MDGs) were screened by a joint analysis of methylome and tr ...[more]

PMID: 35637633

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Project description:Hepatocellular carcinoma (HCC) is the main cause of mortality in patients with chronic viral hepatitis (CVH). We determined the impact of surveillance and treatments on long-term outcomes in patients with CVH who developed HCC. Between 1984 and 2014, 333 patients with HCC and with hepatitis B or hepatitis C virus infection were evaluated. An adjusted lead time bias interval was added to patients with HCC who presented with HCC (no surveillance), and their survival was compared to patients whose HCC was detected by surveillance. After HCC treatments, survival rates within and beyond 3 years of follow-up were compared. In 175 (53%) patients, HCC was detected through surveillance using alpha-fetoprotein and abdominal ultrasound examinations. Compared to 158 (47%) patients with HCC who had no surveillance, more patients with HCC detected by surveillance received surgical and locoregional treatments (P < 0.0001 to P < 0.001), and their 1-, 3-, and 5-year overall and disease-free survival rates were significantly higher (P < 0.001 for both). During the first 3 years of follow-up, patients with HCC receiving liver transplantation had similar survival rates as those with liver resection or radiofrequency ablation (RFA); however, due to HCC recurrence, survival in resection and RFA patients became significantly less when followed beyond 3 years (P = 0.001 to P = 0.04). Factors associated with mortality included tumors beyond University of California at San Francisco criteria (hazard ratio [HR] 2.02; P < 0.0001), Child-Pugh class B and C (HR, 1.58-2.26; P = 0.043 to P = 0.015, respectively), alpha-fetoprotein per log ng/mL increase (HR, 1.30; P < 0.0001), previous antiviral therapy in hepatitis B virus patients (HR, 0.62; P = 0.032), and treatments other than liver transplantation (HR, 2.38-6.45; P < 0.0001 to P < 0.003). Conclusion. Patients with HCC detected by surveillance had prolonged survival. Due to HCC recurrence, survival rates after liver resection and RFA were lower when followed beyond 3 years after treatments. (Hepatology Communications 2017;1:595-608).

Project description:BackgroundThe current Union International Committee on Cancer or the American Joint Committee on Cancer TNM stage system has shown valuable but insufficient estimation for subsets of gastric cancer and prediction for prognosis patients. Thus, there is an urgent need to identify diagnostic, prognostic, and predictive biomarkers to improve patients' outcomes. Our aim was to perform an integrative analysis on publicly available datasets to identify epigenetic changes that may play key role in the initiation and progression of gastric cancer, based on which we set to develop a DNA methylation signature to improve survival prediction of gastric cancer.ResultsA total of 340 methylation-related differentially expression genes (mrDEGs) were screened in gastric cancer patients from The Cancer Genome Atlas (TCGA) project. Pathway enrichment analysis revealed that they were involved in the biological process related to initiation and progression of gastric cancer. Based on the mrDEGs identified, we developed a DNA methylation signature consisting of ten gene members (SCNN1B, NFE2L3, CLDN2, RBPMS2, JPH2, GBP6, COL4A5, SMKR1, PPP1R14A, and ARL4D) according to their methylation β value. This innovative DNA methylation signature was associated with cancer recurrence, while it showed independence of cancer recurrence and TNM stage for survival prediction. Combination of this DNA methylation signature and TNM stage improved overall survival prediction in the receiver operating characteristic analysis. We also verified that two individual genes (PPP1R14A and SCNN1B) of the identified prognostic signature were regulated by promoter region methylation in a panel of gastric cell lines.ConclusionsThis study presents a powerful DNA methylation signature by performing analyses integrating multi-source data including transcriptome, methylome, and clinical outcome of gastric cancer patients from TCGA. The identified DNA methylation signature may be used to refine the current prognostic model and facilitate further stratification of patients in the future clinical trials. Further experimental studies are warranted to unveil the regulatory mechanism and functional role of all the individual genes of the DNA methylation signature. Also, clinical investigations in large GC patient cohorts are greatly needed to validate our findings.

Dataset Information

A novel DNA methylation-driver gene signature for long-term survival prediction of hepatitis-positive hepatocellular carcinoma patients.

Background

Methods

Results

Conclusions

Publications

A novel DNA methylation-driver gene signature for long-term survival prediction of hepatitis-positive hepatocellular carcinoma patients.

Similar Datasets

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