Integrated Proteomics and Bioinformatics to Identify Potential Prognostic Biomarkers in Hepatocellular Carcinoma

Abstract

Background

Liver hepatocellular carcinoma (HCC) is the third most common cause of death by cancer and has a high mortality world-widely. Approximately 75–85% of primary liver cancers are caused by HCC. Uncovering novel genes with prognostic significance would shed light on improving the HCC patient’s outcome.

Objective

In this research, we aim to identify novel prognostic biomarkers in hepatocellular carcinoma.

Methods

Integrated proteomics and bioinformatics analysis were performed to investigate the expression landscape of prognostic biomarkers in 24 paired HCC patients.

Results

As a result, eight key genes related to prognosis, including ACADS, HSD17B13, PON3, AMDHD1, CYP2C8, CYP4A11, SLC27A5, CYP2E1, were identified by comparing the weighted gene co-expression network analysis (WGCNA), proteomic differentially expressed genes (DEGs), proteomic turquoise module, The Cancer Genome Atlas (TCGA) cohort DEGs of HCC. Furthermore, we trained and validated eight pivotal genes integrating these independent clinical variables into a nomogram with superior accuracy in predicting progression events, and their lower expression was associated with a higher stage/risk score. The Gene Set Enrichment Analysis (GSEA) further revealed that these key genes showed enrichment in the HCC regulatory pathway.

Conclusion

All in all, we found that these eight genes might be the novel potential prognostic biomarkers for HCC and also provide promising insights into the pathogenesis of HCC at the molecular level.

Keywords:

• hepatocellular carcinoma
• HCC
• proteomics
• bioinformatics analysis
• prognosis
• biomarkers

Abbreviations

HCC, hepatocellular carcinoma; WGCNA, weighted gene co-expression network analysis; DEGs, Differentially expressed genes; TCGA, The Cancer Genome Atlas; PPI, Protein-Protein Interaction; GO, Gene Ontology; KEGG, Kyoto Encyclopedia of Genes and Genomes; GSEA, the gene set enrichment analysis; FDR, false discovery rate.

Data Sharing Statement

All datasets generated for this study are included in the article.

Ethics Statement

Our study was approved by the Protection of Human Subjects Committee of Nanfang Hospital (approval no. NFEC-201801-K4). We obeyed the principles of the 1983 Declaration of Helsinki. All experiments in this paper obeyed this principle.

Disclosure

The authors declare that they have no competing interests.