Analysis of microsatellite instability differences in eight types of tumors.

Abstract

e15174 Background: Microsatellite instability-high (MSI-H) is the gain or loss of nucleotides from repetitive DNA caused by genomic hypermutability and a powerfully predictive phenotype for diagnosis, immunotherapy and prognosis in various types of cancer. Herein, we analyze the frequency of MSI-H for the understanding of epidemiology of MSI-H across major types of human cancer. Methods: MSI value was calculated by bioinformatics algorithm based on NGS from 539 genes panel in tumor tissue. Patients were divided into three classes as MSI-H, MSI-L and MSS based on MSI value. MSI-H was defined as above 10% positive of the 195 tested microsatellites sites, and this method was totally consistent with conventional MSI-PCR testing in research and development sample verification. We compared the differences of MSI-H ratio in eight types of human cancer including liver cancer, bile duct cancer, gastric cancer, colorectal cancer, pancreatic cancer, melanoma, glioma and lung cancer from 874 cancer cases via χ2 test, adjusted standardized residual or Fisher's exact test. Results: The ratios of MSI-H in eight types of solid tumors were 0% in 32 patients with bile duct cancer or 27 patients with pancreatic cancer, 0.6% (1/174) in liver cancer, 1.9% (1/54) in gastric cancer, 6.7% (8/119) in colorectal cancer, 3.1% (1/32) in melanoma, 4% (1/25) in glioma, and 0.5% (2/411) in lung cancer, respectively. Significant correlations between the MSI-H and cancer types were found by χ2 test (χ2 = 26.571, Cramer’s V coefficient = 0.174, p = 3.980×10−4). Only patients with colorectal cancer had absolute values of adjusted standardized residual above 3, its observed counts of MSI-H significantly higher than expected counts. Fisher’s exact test was performed to analyze the differences of MSI-H ratio across hepatobiliary (liver and bile duct) cancer, digestive tract (gastric and colorectal) cancer and lung cancer, and we found the MSI-H ratio of patients with digestive duct cancer was significantly higher than patients with hepatobiliary cancer ( p = 0.007) or lung cancer ( p = 4.599×10−4). Conclusions: Our study provided new references to cancer-specific properties and clinical diagnosis of MSI especially in East Asian populations. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.