Background Increasing evidence indicates that RAD50, which is involved in the DNA double-strand break (DSB) repair process, is also involved in cancer outcomes. However, its role in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) remains unclear.Aim This study was designed to investigate the expression of RAD50 and its prognostic value in HCC patients.
Method A total of 207 patientswith HBV-associated HCCfrom two cohorts (107 and 100 patientsfrom the Affiliated Hospital of Youjiang Medical University of Nationalities and the Affiliated Hospital of Nantong University, respectively) were enrolled in the current study.The distribution of the categorical clinical-pathological data and the levels of RAD50 expression were compared with a χ 2 test. IHC staining of RAD50 was performed.A partial likelihood test based onunivariate 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 TCGA cohort. The validation analysis indicated that significantly increased levels of RAD50 were expressed in HCC tissues in the two independent cohorts, AHYMUN and AHNTU. In addition, HCC patients with elevated RAD50 expression levels showed poor OS and DFSin the AHYMUN cohort and decreased OS and DF Sin the AHNTU cohort. Furthermore, four datasets obtained from the Oncomine database validated the analysis of the differential expression of RAD50 in HCC tumours and normal tissues.
Discussion In our study, we demonstrated that RAD50 was positively correlated with poor prognosis in HCC patients in the TCGA cohort. Our study also suggested that increased RAD50 expression in HBV-related HCC is a marker of poor prognosis. In this study, the analysis of the data form the two cohorts supported our hypothesis and clearly demonstrated thehigh expression of RAD50 in tumour tissues from HCC patients, which results inincreases in the HCC recurrence rate and poor overall survival.