Jin Xiaojun, Song Yongfei, An Zhanglu, Wu Shanshan, Cai Dihui, Fu Yin, Zhang Chuanjing, Chen Lichao, Tang Wen, Zheng Zequn, Lu Hongsheng, Lian Jiangfang
School of Medicine, Ningbo University, Ningbo, China.
Department of Cardiovasology, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China.
Front Oncol. 2022 Apr 26;12:868411. doi: 10.3389/fonc.2022.868411. eCollection 2022.
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.
目前的肿瘤-淋巴结-转移（TNM）系统在预测肝细胞癌（HCC）患者的生存和指导治疗方面存在局限性，因为TNM系统仅关注解剖学因素，而忽略了肿瘤内分子的异质性。此外，肿瘤内免疫基因格局已成为一种预后指标。中介体复合物亚基8（MED8）是一种主要的聚合酶调节因子，在肾细胞癌中被描述为一种癌基因，但其在HCC中的病理生理意义及其对HCC预后的贡献仍不清楚。在此，我们旨在探讨MED8在HCC中的表达谱及临床相关性，并构建基于MED8相关免疫调节因子的预测模型，作为TNM系统的补充。根据我们的分析，MED8在HCC组织中过表达，MED8表达增加是HCC预后不良的一个指标。敲低MED8可减弱HepG2和Huh7细胞的增殖、集落形成和迁移能力。随后，利用癌症基因组图谱（TCGA）数据库基于一组三个与MED8相关的免疫调节因子确定了一个预测模型，并在国际癌症基因组联盟（ICGC）数据库中进一步验证。该预测模型与TNM系统相结合可提高预测HCC患者生存的性能。在TCGA和ICGC数据库中，以及在早期临床病理分类的亚组分析中，高危患者的总生存期较差。还发现高危患者在TCGA队列中有更高的复发概率。此外，低风险评分表明对免疫治疗和药物治疗有更好的反应。这种预测模型可作为TNM系统的补充，可能对HCC的预后分层和治疗指导有意义。
