Correlation between TMB and MSI in patients with solid tumors.

Abstract

e15169 Background: Both oftumor mutational burden (TMB) and microsatellite instability (MSI) are promising predictive biomarkers for immunotherapy in cancer treatment. However, the association between TMB and MSI with solid tumors was not well investigated especially in East Asian patients. Herein, the relationships for characterizing TMB and MSI in major cancer types were made. Methods: TMB and MSI were measured by 539 genes panel via NGS in tumor tissues. The TMB were calculated as the numbers of synonymous and nonsynonymous mutations, and InDels per megabase in coding regions. MSI was the gain or loss of nucleotides from repetitive DNA and the criteria of MSI-H were 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. The relationships between TMB and MSI of 874 patients with solid tumors including 174 patients with liver cancer, 32 patients with bile duct cancer, 54 patients with gastric cancer, 119 patients with colorectal cancer, 27 patients with pancreatic cancer, 32 patients with melanoma, 25 patients with glioma and 411 patients with lung cancer cases were performed by Spearman rank correlation analysis via SPSS v22.0. Results: There was no significant correlation between TMB and MSI in total patients with solid tumors (r = 0.061, p = 0.073). Significantly correlations were observed in patients with colorectal cancer (r = 0.248, p = 0.006) and pancreatic cancer (r = 0.397, p = 0.040). Meanwhile, no significant correlations between TMB and MSI were identified in patients with liver cancer (r = -0.016, p = 0.830), bile duct cancer (r = 0.325, p = 0.070), gastric cancer (r = 0.209, p = 0.130), melanoma (r = -0.057, p = 0.757), glioma (r = 0.009, p = 0.967) and lung cancer (r = 0.015, p = 0.758). Interestingly, total eleven cases were confirmed as MSI high in patients with colorectal cancer, glioma and lung cancer all presented phenotypes of TMB high. Conclusions: We demonstrated the presence of tumor-specific properties correlations between TMB and MSI and provided new insights to use them as biomarkers in immunotherapy. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.