Association of LRP1B mutants with immune biomarkers in Chinese non-small cell lung cancer patients.

Abstract

e21060 Background: LRP1B (low-density lipoprotein receptor-related protein 1B) is frequently mutated in non-small cell lung cancer (NSCLC). Previous studies showed LRP1B mutations were associated with prolonged survival in melanoma and NSCLC immunotherapy cohort. Higher tumor mutation burden was found in LRP1B mutated patients, suggesting potential benefit of immunotherapy. Herein, we investigate the relationship of LRP1B and immunotherapy biomarker in lager cohort of Chinese and Western NSCLC patients. Methods: Next-generation sequencing data and clinical data were collected from 1053 TCGA NSCLC patients (Western cohort). A 539-gene panel targeted sequencing assay was performed on FFPE tumor samples from 1056 Chinese pan-cancer patients (Chinese cohort). Both LRP1B mutation ratio and TMB were calculated on the two cohorts following the same criteria. TMB-H was defined as the top quartile of all TMB values. Results: In total, 208 (20%) of the 1056 Chinese patients and 385 (37%) of the 1053 Western patients had at least one mutation of LRP1B genes (LRP1B mutant group). The frequency of LRP1B mutation between Western cohort and Chinese cohort had significant difference (20% vs. 37%, p＜0.001). In both cohorts, TMB was higher in the LRP1B mutant group compared to non-LRP1B mutant group. In Chinese cohort, PD-L1 positive was not associated with LRP1B mutation. Patients with LRP1B mutation were associated with prolonged survival in Western immunotherapy cohort. Conclusions: Our study provided a landscape of LRP1B mutations in a much larger Chinese NSCLC group, which could be a valuable complement to TCGA dataset and previous study. Results of our study was consistent with previous studies. Both in Chinese and Western cohorts, the higher TMB in LRP1B mutant patients suggested potential efficacy from immunotherapy of LRP1B mutant group. This result and the potential predictive value of LRP1B in immunotherapy should be validation in a larger Chinese LRP1B mutant cohort in the further.