High Expression of Mediator Complex Subunit 8 Acts as a Prognostic Biomarker in Hepatocellular Carcinoma

Abstract

Background : Mediator complex subunit 8 ( MED8 ) encodes a subunit of the mediator complex ( MED ), which is critical for transcription. MED8 is highly expressed in some tumours and is associated with a poor prognosis. However, correlations between MED8 and clinical features of hepatocellular carcinoma (HCC) have not been reported. Results: A univariate analysis showed that high MED8 expression predicts poor overall survival (HR: 2.495; 95% confidence interval (CI) 1.740, 3.578; P < 0.001). A multivariate regression analysis showed that high MED8 (HR: 3.032 (1.817, 5.060); P < 0.001) expression and M stage (HR=4.075 (1.179-14.091) for M1 vs. M0, P=0.026) are independent prognostic indicator of poor overall survival in patients with HCC. The areas under the curve (AUC) for receiver operating characteristic (ROC) curves were used to describe the prognostic value of MED8 (AUC: 0.905 (0.849, 0.941)). Gene Set Enrichment Analysis (GSEA) and Immune infiltration Analysis were applied to reveal significant enrichment differences among TCGA data. A functional analysis showed that the cell cycle checkpoints, mitotic G2-G2–M phases, transcriptional regulation by TP53, and regulation of TP53 activity were significantly enriched in DEGs associated with high MED8 expression. Th2 cells were positively correlated with MED8 expression. Conclusions: MED8 predicts poor prognosis in HCC, potentially via the regulation of the cell cycle regulation and Th2 cells. Key words: Mediator complex subunit 8, Mediator , hepatocellular carcinoma, prognosis, diagnostic biomarker

Unraveling the underlying pathogenic factors driving nonalcoholic steatohepatitis and hepatocellular carcinoma: an in-depth analysis of prognostically relevant gene signatures in hepatocellular carcinoma

“…The suppression of MED8 led to a notable decrease in the proliferation and migration of HepG2 and Huh7 cells [ 83 ]. Further investigation has elucidated that MED8 plays a crucial role in determining a poor prognosis in HCC, principally by promoting cancer progression through the activation of TH2 cytokines [ 84 ]. YBX1, sometimes referred to as YB-1, is a versatile RNA-binding protein that possesses the evolutionarily conserved Cold-shock Domain (CSD) [ 85 ].…”