A four-methylated mRNA signature-based risk score system predicts survival in patients with hepatocellular carcinoma

Abstract

Evidence suggests that altered DNA methylation plays a causative role in the pathogenesis of various cancers, including hepatocellular carcinoma (HCC). Thus, methylated differently expressed genes (MDEGs) could potentially serve as biomarkers and therapeutic targets in HCC. In the present study, screening four genomics profiling datasets (GSE62232, GSE84402, GSE73003 and GSE57956) enabled us to identify a total of 148 MDEGs. A signature was then established based on the top four MDEGs (BRCA1, CAD, CDC20 and RBM8A). Taking clinical variables into consideration, we constructed a risk score system consisting of the four-MDEG signature and the patients’ clinical features, which was predictive of prognosis in HCC. The prognostic value of the HCC risk score system was confirmed using TCGA HCC samples. The scores were then used to construct a nomogram, performance of which was evaluated using Harrel’s concordance index (C-index) and a calibration curve. The signature-based nomogram for prediction of overall survival in HCC patients exhibited good performance and was superior to traditional staging systems (C-index: 0.676 vs 0.629, P< 0.05). We have thus established a novel risk score system that is predictive of prognosis and is a potentially useful guide for personalized treatment of HCC patients.

A Nomogram Based on a Three-Gene Signature Derived from AATF Coexpressed Genes Predicts Overall Survival of Hepatocellular Carcinoma Patients

“…Meanwhile, gene signatures can provide clues of potential therapeutic targets to improve clinical outcomes of HCC. Many prognostic gene signatures including mRNA, miRNA, or lncRNA were identified in previous studies, and the gene number of these gene signatures may be different [15][16][17][18][19][20][21][22][23]. In the present study, AATF, a key transcription factor contributing to the occurrence and development of HCC, was used to identify coexpressed genes which may play an important role in the molecular mechanisms in the AATF regulation process of gene transcription [24].…”

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

“…The classification was based on the caret R package. To confirm the prognostic value of 8 MDGs, the Uni-variate cox regression, LASSO cox regression, and Multi-variate cox regression algorithms were performed in the training set and a potential risk signature of non-viral HCC was developed (Bøvelstad et al, 2007;Qiu et al, 2017;Wang et al, 2019). The risk score for the signature (Lossos et al, 2004) was computed using the formula:…”

“…In addition, six MDGs, including SNHG6, S100P, DCDC2, LIME1, FMO3, and GPR171, have been selected to construct a predictive signature for HCC patients and the contribution of virus infection has been highly emphasized in their work (Li et al, 2019). Wang et al also constructed a risk score system consisting of BRCA1 expression, CAD expression, RBM8A expression and CDC20 expression by using four GSE data (Wang et al, 2019). However, a novel methylation prognostic signature for non-viral HCC still remains undeveloped and a systematic exploration of non-viral HCC signature is needed.…”

Mining Prognostic Biomarkers of Hepatocellular Carcinoma Based on Immune-Associated Genes

“…MiR-345 a novel biomarker in diagnosis and treatment is useful in HCC prognosis due to its function in the inhibition of tumor metastasis and epithelial-mesenchymal transition (Yu et al, 2017). Wang et al (2019) developed a novel four-methylated mRNA signature-based risk score system, which was used in predicting prognosis and a useful guide for individualized treatment in HCC patients.…”