Abstract 5098: Genetic and immunologic characteristics of biliary tract cancer patients with LRP1B mutation

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Abstract Background: Although the initial clinical results of immune checkpoint inhibitors (ICI) have been obtained in biliary tract cancer (BTC), and previous researches explored potential biomarkers for predicting response to ICI in BTC, and gene LRP1B was found as one of predictive biomarkers. Here we evaluated the mutation information of LRP1B in Chinese patients with BTC, and analyzed the potential explanation for more benefit from ICI treatment in patients with LRP1B mutation. Methods: The formalin-fixed paraffin-embedded specimens of 1324 cancer patients who have underwent next-generation sequencing (NGS) from 2016 to 2021, were included in this study. NGS was performed to detect gene mutation, and tumor mutational burden (TMB) measured by a 733 gene panel. PD-L1 expression detected by using Dako PD-L1 IHC 22C3 pharmDx. Result: The NGS results revealed that 12.76% (169/1324) patients with BTC have LRP1B mutation. Among these 1324 patients, 931 (patients with or without LRP1B mutations were 129 and 802, respectively) patients were available for analysis of TMB level, 820 ((patients with or without LRP1B mutations were 114 and 706, respectively)) patients for analysis of PD-L1 expression, and 1163 (patients with or without LRP1B mutations were 172 and 991, respectively) patients for analysis of MSI-H. TMB level and PD-L1 expression level were compared between groups with and without LRP1B mutation, and results showed that both these two biomarkers were higher in group with LRP1B mutation than without LRP1B mutation, especially TMB level was significantly higher (p<0.001).Further analysis revealed that the median TMB level, proportion of strong positive PD-L1 expression, and proportion of MSI-H were all higher in group of LRP1B mutation than wild type. Conclusion:These results suggest that LRP1B can be considered as one of effective biomarkers for ICI treatment in BTC, the underly mechanism may be related to the high TMB level. Citation Format: Weiwei Chen, Hushan Zhang, Hongmin Dong, Gang Wang, Xiaokai Li, Wanghua Chen, Guodong Li, Saixi Bai, Juan Chen, Wenling Wang. Genetic and immunologic characteristics of biliary tract cancer patients with LRP1B mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5098.

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