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Open Access 01-12-2021 | Hepatocellular Carcinoma | Research article

Integrated analysis of methylation-driven genes and pretreatment prognostic factors in patients with hepatocellular carcinoma

Authors: Dongsheng He, Shengyin Liao, Lifang Cai, Weiming Huang, Xuehua Xie, Mengxing You

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

The potential reversibility of aberrant DNA methylation indicates an opportunity for oncotherapy. This study aimed to integrate methylation-driven genes and pretreatment prognostic factors and then construct a new individual prognostic model in hepatocellular carcinoma (HCC) patients.

Methods

The gene methylation, gene expression dataset and clinical information of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Methylation-driven genes were screened with a Pearson’s correlation coefficient less than − 0.3 and a P value less than 0.05. Univariable and multivariable Cox regression analyses were performed to construct a risk score model and identify independent prognostic factors from the clinical parameters of HCC patients. The least absolute shrinkage and selection operator (LASSO) technique was used to construct a nomogram that might act to predict an individual’s OS, and then C-index, ROC curve and calibration plot were used to test the practicability. The correlation between clinical parameters and core methylation-driven genes of HCC patients was explored with Student’s t-test.

Results

In this study, 44 methylation-driven genes were discovered, and three prognostic signatures (LCAT, RPS6KA6, and C5orf58) were screened to construct a prognostic risk model of HCC patients. Five clinical factors, including T stage, risk score, cancer status, surgical method and new tumor events, were identified from 13 clinical parameters as pretreatment-independent prognostic factors. To avoid overfitting, LASSO analysis was used to construct a nomogram that could be used to calculate the OS in HCC patients. The C-index was superior to that from previous studies (0.75 vs 0.717, 0.676). Furthermore, LCAT was found to be correlated with T stage and new tumor events, and RPS6KA6 was found to be correlated with T stage.

Conclusion

We identified novel therapeutic targets and constructed an individual prognostic model that can be used to guide personalized treatment in HCC patients.

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Title: Integrated analysis of methylation-driven genes and pretreatment prognostic factors in patients with hepatocellular carcinoma
Authors: Dongsheng He
Shengyin Liao
Lifang Cai
Weiming Huang
Xuehua Xie
Mengxing You
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Hepatocellular Carcinoma
Hepatocellular Carcinoma
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08314-5

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Abstract

Background

Methods

Results

Conclusion

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