Comprehensive analysis reveals a metabolic ten-gene signature in hepatocellular carcinoma

Abstract

Background Due to the complicated molecular and cellular heterogeneity in hepatocellular carcinoma (HCC), the morbidity and mortality still remains high level in the world. However, the number of novel metabolic biomarkers and prognostic models could be applied to predict the survival of HCC patients is still small. In this study, we constructed a metabolic gene signature by systematically analyzing the data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC). Methods Differentially expressed genes (DEGs) between tumors and paired non-tumor samples of 50 patients from TCGA dataset were calculated for subsequent analysis. Univariate cox proportional hazard regression and LASSO analysis were performed to construct a gene signature. The Kaplan–Meier analysis, time-dependent receiver operating characteristic (ROC), Univariate and Multivariate Cox regression analysis, stratification analysis were used to assess the prognostic value of the gene signature. Furthermore, the reliability and validity were validated in four types of testing cohorts. Moreover, the diagnostic capability of the gene signature was investigated to further explore the clinical significance. Finally, Go enrichment analysis and Gene Set Enrichment Analysis (GSEA) have been performed to reveal the different biological processes and signaling pathways which were active in high risk or low risk group. Results Ten prognostic genes were identified and a gene signature were constructed to predict overall survival (OS). The gene signature has demonstrated an excellent ability for predicting survival prognosis. Univariate and Multivariate analysis revealed the gene signature was an independent prognostic factor. Furthermore, stratification analysis indicated the model was a clinically and statistically significant for all subgroups. Moreover, the gene signature demonstrated a high diagnostic capability in differentiating normal tissue and HCC. Finally, several significant biological processes and pathways have been identified to provide new insights into the development of HCC. Conclusion The study have identified ten metabolic prognostic genes and developed a prognostic gene signature to provide more powerful prognostic information and improve the survival prediction for HCC.

Identification of a Novel Four-Gene Signature Correlated With the Prognosis of Patients With Hepatocellular Carcinoma: A Comprehensive Analysis

“…Several prior analyses have also shown that certain gene signatures may predict patient survival (20)(21)(22)(23)(24)(25)(26); however, our study has some differences and/or advantages compared with similar analyses. First, the gene signatures built in previous studies require many genes (20)(21)(22)(23), which possibly leads to some difficulties in real-world practice. Our novel signature requires only 4 genes, and the predictive ability of our signature is acceptable, which increases the feasibility of the use of our signature in real-world practice.…”

Construction and validation of a metabolic risk model predicting prognosis of colon cancer

“…Most of the genes have been proved to take part in pathogenesis, progression and prognosis of cancers. We compared this metabolic risk model with other metabolic signatures in previous studies and found that PAFAH1B3 is a good prognostic gene in myelogenous leukemia 26 while LPCAT1 is a risky prognostic gene in hepatocellular carcinoma 27 , which has the same function in colon cancer. Platelet activating factor acetyl hydrolase 1B3 (PAFAH1B3) is involved in ether lipid metabolism, and was reported to play an important role in tumorigenesis and aggressiveness in many different cancers 28 .…”

Risk Signature Related to Immunotherapy Reaction of Hepatocellular Carcinoma Based on the Immune-Related Genes Associated With CD8+ T Cell Infiltration

“…In recent years, the identification of prognostic gene signature for HCC has been noted in many researches ( Chen et al, 2020 ; Hu et al, 2020 ; Zhu et al, 2020 ). However, to the best of our knowledge, none of them constructed a risk signature based on IRGs related to CD8 + T cells.…”