A FITM1-Related Methylation Signature Predicts the Prognosis of Patients With Non-Viral Hepatocellular Carcinoma

Jie Chen; Xicheng Wang; Xining Wang; Wenxin Li; Changzhen Shang; Tao Chen; Yajin Chen

doi:10.3389/fgene.2020.00099

A FITM1-Related Methylation Signature Predicts the Prognosis of Patients With Non-Viral Hepatocellular Carcinoma

Front Genet. 2020 Feb 27:11:99. doi: 10.3389/fgene.2020.00099. eCollection 2020.

Authors

Jie Chen^{1

2}, Xicheng Wang^{1

2}, Xining Wang^{1

2}, Wenxin Li³, Changzhen Shang^{1

2}, Tao Chen^{1

2}, Yajin Chen^{1

2}

Affiliations

¹ Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
² Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
³ Department of Cardiology, The Eight Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.

Abstract

Although great progress has been made in treatment against hepatitis virus infection, the prognosis of hepatocellular carcinoma (HCC) remains unsatisfied. Therefore, there is an unmet need to explore biomarkers or prognostic models for monitoring non-viral hepatocellular carcinoma. Accumulating evidence indicates that DNA methylation participates in carcinogenesis of malignancies. In the present study, we analyzed 101 non-viral HCC patients from TCGA database to figure out methylation-driven genes (MDGs) that might get involved in non-viral HCC pathogenesis using MethyMix algorithm. Then we picked out 8 key genes out of 137 MDGs that could affect the overall survival (OS) of both methylation and expression level. Using PCA, Uni-variate, Multi-variate, and LASSO cox regression analyses, we confirmed the potential prognostic value of these eight epigenetic genes. Ultimately, combined with immunohistochemistry (IHC), ROC, OS, and GSEA analyses, fat storage-inducing transmembrane protein1 (FITM1) was identified as a novel tumor suppressor gene in non-viral HCC and an applicable FITM1-methylation-based signature was built in a training set and validated in a testing set. Briefly, our work provides several potential biomarkers, especially FITM1, as well as a new method for disease surveillance and treatment strategy development.

Keywords: FITM1; methylation-driven genes; nomogram; non-viral hepatocellular carcinoma; signature.