Simple SummaryColorectal cancer (CRC) is the third-most frequent cancer in the world and the second in terms of mortality rate. Consequently, the identification of biomarkers that can be used to predict CRC prognosis is of considerable interest. Proteins involved in the detection and repair of DNA damage have been implicated in the development, evolution, and response to therapy for many cancers, including CRC. In this study, we investigated the prognostic value of one such factor, known as meiotic recombination 11 (MRE11)—a member of an essential DNA repair complex. We found that elevated MRE11 expression was associated with poor overall and disease-free survival, showing high prognostic value for the subgroup of patients with right-sided primary CRC. Collectively, our findings suggest that MRE11 is an independent biomarker in CRC, which can be leveraged to improve patient outcomes.AbstractMeiotic recombination 11 (MRE11) plays a critical role in the DNA damage response and maintenance of genome stability and is associated with the prognosis for numerous malignancies. Here, we explored the clinicopathological significance and prognostic value of MRE11 expression in colorectal cancer (CRC), a leading cause of cancer-related deaths worldwide. Samples from 408 patients who underwent surgery for colon and rectal cancer between 2006 and 2011, including a sub-cohort of 127 (31%) patients treated with adjuvant therapy, were analyzed. In Kaplan–Meier survival analyses, we found that high MRE11 expression in the tumor center (TC) was significantly associated with poor disease-free survival (DFS;p= 0.045) and overall survival (OS;p= 0.039). Intriguingly, high MRE11 expression in the TC was also significantly correlated with reduced DFS (p= 0.005) and OS (p= 0.010) in the subgroup with right-sided primary CRC. In multivariate analyses, high MRE11 expression (hazard ratio [HR] = 1.697, 95% confidence interval [CI]: 1.034–2.785;p= 0.036) and lymphovascular/perineural invasion (LVI/PNI; HR = 1.922, 95% CI 1.122–3.293;p= 0.017) showed significant association with worse OS in patients with right-sided tumors but not those with left-sided tumors. Moreover, in patients with right-sided tumors, high MRE11 was associated with worse OS for those with lymph node involvement (p= 0.006) and LVI/PNI (p= 0.049). Collectively, our results suggest that MRE11 may serve as an independent prognostic marker in those with right-sided severe CRC, with clinical value in the management of these patients.