Elevated double-strand break repair protein RAD50 predicts poor prognosis in hepatitis B virus-related hepatocellular carcinoma: A study based on Chinese high-risk cohorts

Wangrui Liu; Wenhao Xu; Yuyan Chen; Liugen Gu; Xiaolei Sun; Yuanyuan Qu; Hailiang Zhang; Xiaojuan Liu; Haineng Huang

doi:10.7150/jca.46703

Elevated double-strand break repair protein RAD50 predicts poor prognosis in hepatitis B virus-related hepatocellular carcinoma: A study based on Chinese high-risk cohorts

J Cancer. 2020 Aug 14;11(20):5941-5952. doi: 10.7150/jca.46703. eCollection 2020.

Authors

Wangrui Liu^{1

2}, Wenhao Xu^{3

4}, Yuyan Chen⁵, Liugen Gu⁶, Xiaolei Sun⁷, Yuanyuan Qu^{3

4}, Hailiang Zhang^{3

4}, Xiaojuan Liu⁷, Haineng Huang^{1

2}

Affiliations

¹ Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, 533000, China.
² Clinical College of Youjiang Medical University for Nationalities, Baise, Guangxi, 533000, China.
³ Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
⁴ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 20032, China.
⁵ Department of Gastrointestinal Surgery, Nantong University Affiliated Hospital, Nantong, Jiangsu, 226001, China.
⁶ Gastroenterology Department, Second affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, China.
⁷ Department of Pathogenic Biology, Medical College, Nantong University, Nantong, Jiangsu, 226001, China.

Abstract

Objective: Increasing evidence indicates that RAD50, which is involved in the repair process of DNA double-strand break (DSB), is also involved in cancer outcomes. However, its role in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unclear. This study was designed to investigate the expression of RAD50 and its prognostic value in HBV-related HCC patients. Methods: 107 and 100 patients with HBV-related HCC from the Affiliated Hospital of Youjiang Medical University of Nationalities (AHYMUN) and the Affiliated Hospital of Nantong University (AHNU), respectively, were enrolled in the study. The distribution of the categorical clinical-pathological data and the levels of RAD50 expression were compared with a χ² test. Immunohistochemistry (IHC) staining of RAD50 was performed. A partial likelihood test based on univariate and multivariate Cox regression analysis was developed to address the influence of independent factors on disease-free survival (DFS) and overall survival (OS). The Oncomine online database was used to analyse and validate the differential expression of RAD50. The Kaplan-Meier method and a log-rank test were performed to assess the influence of RAD50 on survival at different levels. Results: RAD50 was highly expressed in HCC tissues compared to normal tissues and was significantly correlated with OS in the Cancer Genome Atlas (TCGA) cohort. The validation analysis indicated that significantly increased levels of RAD50 were expressed in HCC tissues in the two independent cohorts. In addition, HCC patients with elevated RAD50 expression levels showed poor OS and DFS in the AHYMUN cohort and decreased OS and DFS in the AHNTU cohort. Conclusion: In conclusion, our study reveals that elevated RAD50 expression is significantly correlated with cancer progression and poor survival in HBV-related HCC patients. These data suggest that RAD50 may act as an oncogene and may serve as a promising target for the therapy of HBV-related HCC patients.

Keywords: DNA repair; RAD50; hepatocellular carcinoma; multiple cohorts; prognosis.