PCK2:A potential Therapeutic Target and Biomarker for Hepatocellular Carcinoma Based on Weighted Gene Co-Expression Network Analysis

Abstract

Background Hepatocellular carcinoma(HCC) is the sixth most common cancer worldwide, and is associated with a high mortality rate and poor treatment efficacy. Therefore, it is important to explore the underlying mechanisms and screen for novel biomarkers and therapeutic targets. Methods HCC and non-tumor microarray data was obtained from the Gene Expression Omnibus(GEO) database and 1,612 differentially expressed genes (DEGs) were identified. The identified DEGs were then further examined using a weighted gene co-expression network analysis (WGCNA). Modules were identified and correlations with clinical parameters were examined to ultimately identify a single highly correlated module containing a single hub gene, phosphoenolpyruvate carboxykinase 2 (PCK2).The genes co-expressed with PCK2 were then examined via Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis and were found to be primarily enriched in the area of energy metabolism. The association between PCK2 expression and prognosis and tumor stage was then further verified by using a HCC dataset obtained from The Cancer Genome Atlas (TCGA) database. Ex vivo examination of HCC and adjacent non-tumor samples via quantitative real-time PCR demonstrated that PCK2 is downregulated in HCC. Additionally, HCC cell lines overexpressing PCK2 exhibited a time-dependent reduction in cellular viability. Results These findings demonstrate that PCK2 is downregulated in HCC and is associated with HCC prognosis and tumorstage, and that PCK2 may affect HCC progression via energy metabolism. Conclusions this study may help to further elucidate possible HCC progression mechanisms and the findings presented here suggest that PCK2 may serve as a potential HCC therapeutic target or biomarker.