High expression of herpes virus entry mediator is associated with poor prognosis in clear cell renal cell carcinoma

American Journal of Cancer Research

Xu Cao¹  Ming Tang²  You Li³ 

[1] Department of Immunology, Army Medical University (Third Military Medical University), Chongqing 400038, China;Department of Nephrology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, China;Department of Nephrology, The Affiliated Second Hospital, Chongqing Medical University, Chongqing 400016, China

关键词: Clear cell renal cell carcinoma;    herpes virus entry mediator;    disease-free survival;    overall survival;    prognostic biomarker;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

Herpes virus entry mediator (HVEM), also called tumor necrosis factor receptor superfamily 14 (TNFRSF14), is highly expressed in various tumor tissues and plays critical roles in tumor biology. However, the role of HVEM in clear cell renal cell carcinoma (ccRCC) is unknown. This study evaluated the clinical importance of HVEM in patients with ccRCC. HVEM expression was assessed in fresh and 140 archived paraffin-embedded ccRCC tissue samples by quantitative RT-PCR, western blot, and immunohistochemical staining. HVEM expression was higher in ccRCC than in paired peritumor tissue. Kaplan-Meier analysis showed that high level of HVEM expression was associated with poor overall survival (OS) and disease-free survival (DFS) in patients with ccRCC (both P < 0.001). Multivariate analysis indicated that HVEM overexpression was independently prognostic of survival in ccRCC patients. Two novel nomogram systems were constructed by integrating HVEM expression and other clinical parameters to predict OS (c-index 0.75) and DFS (c-index 0.74) in these patients, with both having better predictive accuracy than traditional TNM (c-index 0.65 for OS and 0.639 for DFS) and Fuhrman (c-index 0.612 for OS and 0.641 for DFS) systems. In addition, HVEM silencing led to an observable reduction in tumor cells growth in vitro and in vivo. Taken together, these findings indicate that high HVEM expression is a novel and independent adverse predictor of clinical outcomes in patients with ccRCC and that HVEM may be a potential therapeutic target.

【 授权许可】

CC BY-NC