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

Xiaojun Jin; Yongfei Song; Zhanglu An; Shanshan Wu; Dihui Cai; Yin Fu; Chuanjing Zhang; Lichao Chen; Wen Tang; Zequn Zheng; Hongsheng Lu; Jiangfang Lian

doi:10.3389/fonc.2022.868411

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

Front Oncol. 2022 Apr 26:12:868411. doi: 10.3389/fonc.2022.868411. eCollection 2022.

Authors

Xiaojun Jin^{1

2

3}, Yongfei Song^{2

3}, Zhanglu An^{4

5}, Shanshan Wu¹, Dihui Cai¹, Yin Fu¹, Chuanjing Zhang¹, Lichao Chen¹, Wen Tang¹, Zequn Zheng¹, Hongsheng Lu⁵, Jiangfang Lian^{1

2

3}

Affiliations

¹ School of Medicine, Ningbo University, Ningbo, China.
² Department of Cardiovasology, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China.
³ Central Laboratory, Ningbo Institute of Innovation for Combined Medicine and Engineering, Ningbo, China.
⁴ Graduate School, Hebei North University, Zhangjiakou, China.
⁵ Department of Pathology, Taizhou Central Hospital (Taizhou University Affiliated Hospital), Taizhou, China.

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.

Keywords: HCC; MED8; drug therapy; immunomodulator; immunotherapy; prognosis.