<div><p>Background</p><p>Aberrant expression of DNA repair proteins is associated with poor survival in cancer patients. We investigated the combined expression of MRE11 and ATM as a predictive marker of response to radiotherapy in rectal cancer.</p><p>Methods</p><p>MRE11 and ATM expression were examined in tumor samples from 262 rectal cancer patients who underwent surgery for rectal cancer, including a sub-cohort of 54 patients who were treated with neoadjuvant radiotherapy. The relationship between expression of the two-protein panel and tumor regression grade (TRG) was assessed by Mann–Whitney U test and receiver operating characteristics area under curve (ROC-AUC) analysis. The association between expression of the two-protein panel and clinicopathologic variables and survival was examined by Kaplan-Meier methods and Cox regression analysis.</p><p>Results</p><p>A high score for two-protein combined expression in the tumor center (TC) was significantly associated with worse disease-free survival (DFS) (<i>P</i> = 0.035) and overall survival (OS) (<i>P</i> = 0.003) in the whole cohort, and with DFS (<i>P</i> = 0.028) and OS (<i>P</i> = 0.024) in the neoadjuvant subgroup (n = 54). In multivariate analysis, the two-protein combination panel (HR = 2.178, 95% CI 1.115–4.256, <i>P</i> = 0.023) and perineural invasion (HR = 2.183, 95% CI 1.222–3.899, <i>P</i> = 0.008) were significantly associated with DFS. Using ROC-AUC analysis of good versus poor histological tumor response among patients treated preoperatively with radiotherapy, the average ROC-AUC was 0.745 for the combined panel, 0.618 for ATM alone, and 0.711 for MRE11 alone.</p><p>Conclusions</p><p>The MRE11/ATM two-protein panel developed in this study may have clinical value as a predictive marker of tumor response to neoadjuvant radiotherapy, and a prognostic marker for disease-free and overall survival.</p></div
