J Cancer 2019; 10(18):4333-4340. doi:10.7150/jca.31454
Elevated MRE11 expression associated with progression and poor outcome in prostate cancer
1. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032
2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 20032, P.R. China
* Contribute equally
Wang J, Xu WH, Wei Y, Zhu Y, Qin XJ, Zhang HL, Ye DW. Elevated MRE11 expression associated with progression and poor outcome in prostate cancer. J Cancer 2019; 10(18):4333-4340. doi:10.7150/jca.31454. Available from http://www.jcancer.org/v10p4333.htm
Objective: Growing evidence has proved that MRE11, a protein underpinned to be involved in DNA double-strand break (DSB) repair process, is correlated with cancer outcomes. However, its role in prostate cancer (PCa) remains unclear. This study aimed to investigate the expression of MRE11 in tumor tissue and defining its value in predicting prognosis of PCa patients.
Methods: A total of 578 patients from two cohorts were enrolled in this study. Distribution of categorical clinical-pathological data together with levels of MRE11 expression was compared with χ2-test in a contingency table. Immunohistochemical (IHC) staining and evaluation was detected from 78 paired PCa and adjacent normal tissues. Partial likelihood test from univariate and multivariate Cox regression analysis was developed to address the influence of independent factors on disease-free survival (DFS) and overall survival (OS) in two cohorts. The Kaplan-Meier method and log-rank test were performed to assess the survival benefits between discrete levels. Set Enrichment Analysis (GSEA) was performed to select related genes and pathways from The Cancer Genome Atlas (TCGA) database.
Results: In the current study, we demonstrated that MRE11 was highly expressed in PCa compared with normal tissues (P=0.011). In addition, in the TCGA cohort, the median DFS in patients with IHC positive and negative MRE11 expression levels was 24.5 and 30.6 months, and median OS was 28.7 and 33.0 months, respectively. In FUSCC cohort, median DFS in patients with IHC positive and negative MRE11 expression was 28.0 and 35.6 months. Furthermore, survival curves suggested that PCa patients with elevated MRE11 expression levels showed poorer OS (P=0.019) in TCGA cohort and poor DFS (P=0.047) in FUSCC cohort.
Conclusion: In conclusion, our study reveals that elevated MRE11 expression is significantly correlated with cancer progression and poor survival in PCa patients. These data suggest that MRE11 may act as an oncoprotein and a promising prognostic marker for PCa patients.
Keywords: MRE11, DNA repair, homologous recombination, prognosis, prostate cancer