Value of DNA Repair Gene and TP53 Co-mutation in Predicting Effect of Immunotherapy on Lung Adenocarcinoma

Abstract

Objective To explore the value of DNA repair genes (DRGs) in predicting the effect of immunotherapy on lung adenocarcinoma based on second-generation sequencing technology. Methods The data of lung adenocarcinoma were obtained from the Cancer Genome Atlas, including the testing cohort and the validation cohort. In the testing set, according to the cut-off value of tumor mutational burden (TMB) score 15, the patients with lung adenocarcinoma were divided into two groups: the low TMB score group and the high TMB score group. And we analyzed the relation between TMB and the overall survival of lung adenocarcinoma patients. KRAS and TP53 co-mutation was used as the standard control, the differences in the mutation count and TMB score between only DRGs mutation group and KRAS or TP53 co-mutation groups were analyzed. In the validation cohort, the differences between DRGs and KRAS or TP53 co-mutation groups in TMB, tumor neoantigen burden and PFS were analyzed. Results The patients with TP53/DRGs co-mutation had higher mutation count and TMB score than those patients with only TP53 or DRGs mutation (P < 0.05). The patients with TP53/DRGs co-mutation had higher mutation count and TMB score than those patients with KRAS/TP53 co-mutation (P=0.037, P=0.044). In validation cohort analysis, the TP53/DRGs co-mutation patients also showed higher tumor neoantigens, higher TMB and longer progression-free survival than those patients with only TP53 or DRGs or KRAS/TP53 co-mutation groups. Conclusion TP53/DRGs co-mutation may be served as a pair of potential biomarkers for predicting the efficacy of immunotherapy on lung adenocarcinoma.

Keywords

• dna repair gene
• lung adenocarcinoma
• immunotherapy
• biomarker