Study Of MSI Detection In Sporadic Colorectal Cancer And The Correlation With Clinicopathological Features And Other Gene

OBJECTIVES:Colorectal cancer is one of the most frequently diagnosed among many types of malignant tumor, The latest WHO data on the global cancer situation shows that the incidence of colorectal cancer ranked fourth from all cancer and its mortality rate ranked third. Theincidence of colorectal cancer has increased over the year and has become the main disease which endangers human well-being. Currently the occurrence of colorectal cancer is generally considered to be involving genetic and environmental factors built by the interaction of many steps and complex process of multiple genetic alterations. And it is known that the genetic predisposition is most obviously occurs in the malignant lesion of the colorectal cancer. In year 1980, Wyman et al. found microsatellite sequences, and the researchers recognized that hereditary non-polyposis colorectal cancer(HNPCC) has an important association with it. The study found that about 7%-28% of sporadic colorectal cancers have microsatellite instability [1,2]. At the same time, the study also found that the distribution of the microsatellite instability creates unique clinical and pathological features, but the relation between pathological mechanism and the microsatellite instability has not yet been conclusive. According to the NCCN guidelines II of diagnosis and treatment of colorectal cancer in one particular section stated. This research has prepared further exploration of microsatellite instability in colorectal cancer, its clinical and pathological features, role of thymidylate synthase and the relationship between the expressions of related genes while providing follow-up on colorectal cancer prognosis. Another advantage of the present study is as a turning point of the previous microsatellite instability, which were based on basic immunohistochemistry experiments, mismatch repair protein expression indirectly derived microsatellite instability, into newly DNA chip investigation for quantitative analysis of microsatellite instability, which provided more basis for the accuracy of the study.METHOD:Subject: Cases are collected from December 2013 to October 2015 from all patients with resected colorectal cancer in our hospital. After completing the screening based on patients’ case history and pathological laboratory result, patients’ who meet the requirements with stage II colorectal cancer are selected for the study, furthermore, patients who has undergone gene chip microsatellite instability detection done by SUREXAM Company are selected as final subjects of this study.Data Collection: Information were retrieved from The First Affiliated Hospital of Chongqing Medical University Original Electronic Medical Record. All factors related to microsatellite instability clinical and pathological characteristics based on local and international literature, and comprehensive clinical experience(gender, age, BMI, pathological or microscopic feature, gross or macroscopic feature, lesion location, tumor size, diabetes). Data was established and developed using EXCEL spreadsheet, data collection was done while improving the database. Other genetic testing also included in the database.Data Analysis: Through the result of MSI detection, the cases above is classified into MSI-H colorectal cancer group and non-MSI-H(including MSI-L and MSS) colorectal cancer group. Database of pathological information and other genetic data is calculated using statistical analysis, chi-square tests are used to compare pathological feature of MSI-H group and non- MSI-H group, t-test is used to analyze other genes expression in both MSI-H and non-MSI-H groups.RESULT:1.According to the inclusion criteria, exclusion criteria and the integrity of the medical records, 105 cases of patients were screened to meet the requirements, including 62 male, 43female; age ranged between the youngest 35 and oldest 83 years old, mean age 61.70 years old, median age 62 years old, age are normally distributed. The details are as follows:2.Based on microsatellite instability expression: stable microsatellite(MSS) 88 cases, 83.8%; low microsatellite instability(MSI-L) 2 cases, 1.9%; high microsatellite instability(MSI-H) 15 cases, 14.3%.3.Based on clinical pathological feature: there are significant differences(P <0.05) on the degree of tumor differentiation and position of tumor/lesion on MSI-H group compared to a non-MSI-H group, and in both groups: gender, age, BMI, gross/macroscopic tumor, tumor depth of invasion, diabetes status and preoperative tumor marker expression levels are not significantly different.4.Association with other genes: microsatellite state TYMS-RNA expression levels have some relevance, in MSI-H group the TS-RNA was highly expressed(P <0.05); microsatellite status and PIK3CAE2 genes mutation is highly significant(P <0.05), in MSI-H group PIK3CAE2 gene relatively highly mutated compared to the non-MSI-H group which have relatively low proportion of mutations. ERCC1, VEGFR1, VEGFR2, VEGFR3 expression levels were not significantly different, BRAF gene, KRAS gene mutations in the UGT1A1 gene had no significant correlation with MSI.