Background and Aims: Neoadjuvant chemoradiotherapy (nCRT) is the gold standard for the treatment of mid-low locally advanced rectal cancer. Patients achieving pathologic complete remission (pCR) may have a better long-term prognosis. Despite the development of new molecular biology and progress of diagnosis and treatment technologies, there are few potential biomarkers for predicting good pathologic response before nCRT. This study was conducted to investigate the expression of mismatch repair (MMR) proteins in patients with mid-low locally advanced rectal cancer and their relationship with the sensitivity of nCRT.  
Methods: A total of 162 patients with mid-low locally advanced rectal cancer admitted in Gastrointestinal Surgery Department of Tongling People's Hospital from January 2014 to December 2019 were enrolled. All patients underwent surgery following nCRT. The expressions of MMR proteins (MLH1, MSH2, MSH6 and PMS2) in their initial colonoscopic biopsy samples were detected by immunohistochemical staining. The relations of MMR protein expression status with clinical variables and nCRT efficacy [according to the RECIST 1.1 evaluation criteria and tumor regressive grading (TRG) score], as well as the relations of the TRG score with the clinicopathologic factors and MMR protein expression status were analyzed, and the influential factors for pCR were determined by multivariate Logistic regression model.
Results: In the 162 patients, deficient MMR (dMMR) was found in 22 cases (13.4%), including MLH1 protein deletion in 17 cases (10.5%), MSH2 protein deletion in 10 cases (6.2%), MSH6 protein deletion in 8 cases (4.9%) and PMS2 protein deletion in 11 cases (6.8%). Histological type, preoperative clinical stage and TRG score were significantly associated with MMR protein expression status (all P<0.05). The effective rate assessed by RECIST 1.1 in dMMR patients was higher than that in patients with proficient MMR (pMMR) (59.1% vs. 36.4%, P=0.043). The sex age, tumor location, differentiation, histological type, CEA level, synchronous chemotherapy regimen and expressions of MLH1, MSH2, MSH6 and PMS2 proteins were irrelevant to TRG score (all P>0.05), while the clinical T stage, clinical N stage, preoperative clinical stage, and the MMR protein expression status (dMMR or pMMR) were related to TRG score (all P<0.05). Logistic multivariate regression analysis revealed that dMMR was an independent influential factor for pCR of the patients (OR=0.327, 95% CI=0.109–0.984, P=0.047). 
Conclusion: In patients with mid-low locally advanced rectal cancer, the dMMR protein phenotype presented in the tissue of initial colonoscopic biopsy indicates a better nCRT effect, and MMR protein expression status can be used as a predictor of nCRT efficacy for rectal cancer patients.