A Predictive Model for Prognosis and Therapeutic Response in Hepatocellular Carcinoma Based on a Panel of Three MED8-Related Immunomodulators

Abstract

The current tumor-node-metastasis (TNM) system is limited in predicting the survival and guiding the treatment of hepatocellular carcinoma (HCC) patients since the TNM system only focuses on the anatomical factors, regardless of the intratumoral molecule heterogeneity. Besides, the landscape of intratumoral immune genes has emerged as a prognostic indicator. The mediator complex subunit 8 (MED8) is a major polymerase regulator and has been described as an oncogene in renal cell carcinoma, but its pathophysiological significance of HCC and its contribution to the prognosis of HCC remain unclear. Here, we aimed to discuss the expression profile and clinical correlation of MED8 in HCC and construct a predictive model based on MED8-related immunomodulators as a supplement to the TNM system. According to our analyses, MED8 was overexpressed in HCC tissues and increased expression of MED8 was an indicator of poor outcome in HCC. The knockdown of MED8 weakened the proliferation, colony forming, and migration of HepG2 and Huh7 cells. Subsequently, a predictive model was identified based on a panel of three MED8-related immunomodulators using The Cancer Genome Atlas (TCGA) database and further validated in International Cancer Genome Consortium (ICGC) database. The combination of the predictive model and the TNM system could improve the performance in predicting the survival of HCC patients. High-risk patients had poor overall survival in TCGA and ICGC databases, as well as in subgroup analysis with early clinicopathology classification. It was also found that high-risk patients had a higher probability of recurrence in TCGA cohort. Furthermore, low-risk score indicated a better response to immunotherapy and drug therapy. This predictive model can be served as a supplement to the TNM system and may have implications in prognosis stratification and therapeutic guidance for HCC.

Detecting early‐warning biomarkers associated with heart‐exosome genetic‐signature for acute myocardial infarction: A source‐tracking study of exosome

“…The molecular subgroups can only be detected from patients' transcriptomes which, in turn, map to distinctive clinical phenotypes through consensus clustering 11 . Increasing studies demonstrate that the heterogeneity of disease molecules influences local cell function, clinical outcomes and therapy response 22,23 . For example, in an analysis of lower‐grade glioma samples, three immune subgroups were found to have different genetic alterations and lymphocyte signatures 24 .…”

“… 11 Increasing studies demonstrate that the heterogeneity of disease molecules influences local cell function, clinical outcomes and therapy response. 22 , 23 For example, in an analysis of lower‐grade glioma samples, three immune subgroups were found to have different genetic alterations and lymphocyte signatures. 24 Additionally, an exploration was performed into the classification of AMI based on early‐warning biomarker profiling to facilitate better stratification of patients with AMI responsive to clinical therapy.…”

Dietary Zn Deficiency Inhibits Cell Proliferation via the GPR39-Mediated Suppression of the PI3K/AKT/mTOR Signaling Pathway in the Jejunum of Broilers

“…Cell proliferation plays an important role in maintaining intestinal integrity and barrier function [ 7 ]. The PCNA is considered to be a marker of cell proliferation in various tissues [ 9 ]. Shao et al [ 10 ] and Kang et al [ 37 ] reported that Zn could increase the number of PCNA-positive cells in the Caco-2 cells or mice.…”

“…Cell proliferation is crucial for preserving the integrity and function of the small intestine [ 8 ]. The number of proliferating cell nuclear antigen (PCNA)-positive cells is considered to be a biomarker of cell proliferation in various tissues [ 9 ]. Shao et al [ 10 ] reported that Zn deficiency decreased PCNA-positive cells in the Caco-2 cells of mice.…”

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

“…The level of MED8 expression was observed to be elevated in HCC tissues. 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 ].…”