Mining prognostic markers of Asian hepatocellular carcinoma patients based on the apoptosis-related genes

Junbin Yan,Jielu Cao,Zhiyun Chen

doi:10.1186/s12885-021-07886-6

Abstract

BackgroundApoptosis-related genes(Args)play an essential role in the occurrence and progression of hepatocellular carcinoma(HCC). However, few studies have focused on the prognostic significance of Args in HCC. In the study, we aim to explore an efficient prognostic model of Asian HCC patients based on the Args.MethodsWe downloaded mRNA expression profiles and corresponding clinical data of Asian HCC patients from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The Args were collected from Deathbase, a database related to cell death, combined with the research results of GeneCards、National Center for Biotechnology Information (NCBI) databases and a lot of literature. We used Wilcoxon-test and univariate Cox analysis to screen the differential expressed genes (DEGs) and the prognostic related genes (PRGs) of HCC. The intersection genes of DEGs and PGGs were seen as crucial Args of HCC. The prognostic model of Asian HCC patients was constructed by least absolute shrinkage and selection operator (lasso)- proportional hazards model (Cox) regression analysis. Kaplan-Meier curve, Principal Component Analysis (PCA) analysis, t-distributed Stochastic Neighbor Embedding (t-SNE) analysis, risk score curve, receiver operating characteristic (ROC) curve, and the HCC data of ICGC database and the data of Asian HCC patients of Kaplan-Meier plotter database were used to verify the model.ResultsA total of 20 of 56 Args were differentially expressed between HCC and adjacent normal tissues (p < 0.05). Univariate Cox regression analysis showed that 10 of 56 Args were associated with survival time and survival status of HCC patients (p < 0.05). There are seven overlapping genes of these 20 and 10 genes, including BAK1, BAX, BNIP3, CRADD, CSE1L, FAS, and SH3GLB1. Through Lasso-Cox analysis, an HCC prognostic model composed of BAK1, BNIP3, CSE1L, and FAS was constructed. Kaplan-Meier curve, PCA, t-SNE analysis, risk score curve, ROC curve, and secondary verification of ICGC database and Kaplan-Meier plotter database all support the reliability of the model.ConclusionsLasso-Cox regression analysis identified a 4-gene prognostic model, which integrates clinical and gene expression and has a good effect. The expression of Args is related to the prognosis of HCC patients, but the specific mechanism remains to be further verified.

Highlights

Apoptosis-related genes(Args)play an essential role in the occurrence and progression of hepatocellular carcinoma(HCC)
The results of the screening of prognostic apoptosisrelated differential expressed genes (DEGs) We found that a total of 20 Args were differentially expressed between Hepatocellular Carcinoma (HCC) tissues and adjacent normal tissues (p < 0.05) (Table 2)
Through univariate Cox regression analysis, we found that a total of 10 Args genes were related to the prognosis of HCC patients (p < 0.05) (Table 3)

Summary

Introduction

Apoptosis-related genes(Args)play an essential role in the occurrence and progression of hepatocellular carcinoma(HCC). Few studies have focused on the prognostic significance of Args in HCC. We aim to explore an efficient prognostic model of Asian HCC patients based on the Args. Liver cancer has become one of the common causes of malignancy-related death globally [1], and its incidence is increasing year by year [2]. HCC is usually caused by various risk factors, including hepatitis B virus, hepatitis C virus, fatty liver, alcohol-related cirrhosis, smoking, obesity, different dietary exposures, etc. Because HCC is a highly heterogeneous disease [7, 8], it is difficult to predict the prognosis. HCC is highly prevalent in Asia, and it is challenging to predict prognosis. It is necessary to develop a useful prognostic model for Asian HCC patients

Objectives

Methods

Results

Conclusion