Abstract
PurposeHepatocellular carcinoma (HCC) is a common solid-tumor malignancy with high heterogeneity, and accurate prognostic prediction in HCC remains difficult. This analysis was performed to find a novel prognostic multigene signature.MethodsThe TCGA-LIHC dataset was analyzed for differentially coexpressed genes through weighted gene coexpression network analysis (WGCNA) and differential gene expression analysis. A protein-protein interaction (PPI) network and univariate Cox regression analysis of overall survival (OS) were utilized to identify their prognostic value. Next, we used least absolute shrinkage and selection operator (LASSO) Cox regression to establish a prognostic module. Subsequently, the ICGC-LIRI-JP dataset was applied for further validation. Based on this module, HCC cases were stratified into high-risk and low-risk groups, and differentially expressed genes (DEGs) were identified. Functional enrichment analyses of these DEGs were conducted. Finally, single-sample gene set enrichment analysis (ssGSEA) was performed to explore the correlation between the prognostic signature and immune status.ResultsA total of 393 differentially coexpressed genes were obtained. Forty differentially coexpressed hub genes were identified using the CytoHubba plugin, and 38 of them were closely correlated with OS. Afterward, we established the four-gene prognostic signature with an acceptable accuracy (area under the curve [AUC] of 1-year survival: 0.739). The ICGC-LIRI-JP dataset also supported the acceptable accuracy (AUC of 1-year survival:0.752). Compared with low-risk cohort, HCC cases in the high-risk cohort had shorter OS, higher tumor grades, and higher T stages. The risk scores of this signature still act as independent predictors of OS (P<0.001). Functional enrichment analyses suggest that it was mainly organelle fission and nuclear division that were enriched. Finally, ssGSEA revealed that this signature is strongly associated with the immune status of HCC patients.ConclusionsThe proposed prognostic signature of four differentially coexpressed hub genes has satisfactory prognostic ability, providing important insight into the prediction of HCC prognosis.
Highlights
It is estimated that nearly 42,810 new cases and 30,160 estimated deaths of hepatocellular carcinoma (HCC) will occur in 2020, leading to enormous socioeconomic pressure for HCC patients and their families [1]
SsGSEA revealed that this signature is strongly associated with the immune status of HCC patients
HCC accounts for 85%–90% of all primary liver cancer patients, and its occurrence is strongly associated with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, alcohol consumption, and nonalcoholic steatohepatitis [2]
Summary
It is estimated that nearly 42,810 new cases and 30,160 estimated deaths of hepatocellular carcinoma (HCC) will occur in 2020, leading to enormous socioeconomic pressure for HCC patients and their families [1]. HCC accounts for 85%–90% of all primary liver cancer patients, and its occurrence is strongly associated with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, alcohol consumption, and nonalcoholic steatohepatitis [2]. HCC has high interpatient, intertumoral and intratumoral heterogeneity [3]. Due to the complicated etiologic factors and the high heterogeneity of HCC, it remains difficult to accurately predict the prognosis of HCC patients. There were some similar studies published previously, they usually required many genes in their gene signatures, which may cause some difficulties in real-world practice [5, 6]. It is urgent to find the gene signature involved with less genes for the convenience of real-world practice
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