The clinical value of mismatch repair protein combined with serum tumor markers and Ki-67 proliferation index in the prognostic evaluation of colorectal cancer

Abstract

Background and purpose: Colorectal cancer is one of the most common malignant tumors of digestive system. The incidence of colorectal cancer has increased significantly in China in recent years. Various clinical and pathological indicators are helpful for the diagnosis, clinical staging and prognostic evaluation of colorectal cancer. This study aimed to observe the correlation between the expression of mismatch repair protein and serum tumor markers and Ki-67 proliferation index in colorectal cancer, and to analyze the prognostic value of mismatch repair protein, serum tumor markers and Ki-67 proliferation index. Methods: Data of 234 patients with colorectal cancer were collected after surgery in Huadong Hospital Affiliated to Fudan University from July 2014 to June 2018, and the preoperative serum levels of tumor markers (CEA, CA19-9, CA72-4, CA12-5), Ki-67 proliferation index and mismatch repair protein expression rate in surgical specimens were analyzed, in order to find the relationship between these clinicopathological features and prognosis of colorectal cancer. Results: Among 234 postoperative specimens of colorectal cancer patients, a total of 29 cases (12.4%) had defective expression of mismatch repair protein (dMMR), and 205 cases (87.6%) had normal expression of mismatch repair protein (pMMR). In the correlation analysis of clinicopathological features, there were statistically significant differences in tumor primary site, differentiation type, stage, T stage and lymph node metastasis between dMMR group and pMMR group (P<0.05). In the correlation analysis of the observed indicators, the differences in Ki-67 proliferation index, preoperative CEA and CA72-4 levels between dMMR group and pMMR group were statistically significant (P<0.05). Among the univariate prognostic analyses, the overall survival rate was significantly lower in the lymph node metastasis group and the advanced stage group (P<0.001). There was significant difference in overall survival rate between dMMR group (100%) and pMMR group (83%) (P<0.05). In the prognostic analysis of the preoperative tumor markers, CEA and CA72-4 levels had prognostic value in survival analysis (P<0.05). Multivariate COX regression analysis of 5 variables showed no significant correlation between expression of mismatch repair protein and lymph node metastasis in prognostic analysis, while significant correlation between staging and preoperative CA72-4 level was found in prognostic analysis (P<0.05). It was suggested that staging and preoperative CA72-4 level were the most important risk factors affecting the prognosis of colorectal cancer patients. Conclusion: dMMR was more common in right-sided colon cancer and in poorly differentiated adenocarcinoma and mucinous adenocarcinoma with poor type. T stage was late, while general pathological stage was early. Lymph node metastasis was rare. In dMMR group, Ki-67 proliferation index was mostly below the mean level (<70% expression), most patients had normal preoperative CEA level and elevated preoperative CA72-4 level. The dMMR group had a higher survival rate compared with the pMMR group, and later stage and increased preoperative CA72-4 level were risk factors affecting prognosis of patients. The expression deficiency of mismatch repair protein has certain prognostic value in patients with colorectal cancer.

Keywords

• |mismatch repair protein|serum tumor marker|ki-67 proliferation index|colorectal cancer|prognosis