Discover Mutational Differences Between Lung Adenocarcinoma and Lung Squamous Cell Carcinoma and Search for More Effective Biomarkers for Immunotherapy.

Abstract

Purpose: Lung cancer is a severe malignant tumor. This study aims to more comprehensively characterize lung cancer patients and identify combination markers for immunotherapy.

Patients and methods: We gathered data from 166 lung cancer patients at the Cancer Hospital Affiliated with Xinjiang Medical University. The collected samples underwent NGS sequencing using a panel of 616 genes associated with cancer. Subsequently, data analysis was conducted to identify markers that are more suitable for lung cancer immunotherapy.

Results: In this study, the most common variant genes in LUAD were TP53, EGFR, MST1, KMT2C, RBM10, LRP1B. Meanwhile, the highest mutation frequency genes in LUSC samples were TP53, KMT2D, LRP1B, FAT1, MST1, KMT2C. Mutation frequencies, tumor mutation burden (TMB), PD-L1 expression, and mutant-allele tumor heterogeneity (MATH) values differed between LUAD and LUSC, with LUSC exhibiting higher values than LUAD. Irrespective of LUAD or LUSC, patients with TMB≥10 demonstrated better immunotherapy efficacy compared to patients with TMB<10. Similarly, when PD-L1≥50%, whether in LUAD or LUSC, the immunotherapy effect was superior to that of patients with PD-L1<50%. Combining TMB≥10 and PD-L1≥50% as immunotherapy markers, in both LUAD and LUSC, resulted in a very favorable immunotherapy effect, with the overall response rate (ORR) reaching 100%.

Conclusion: We observed distinct mutation patterns and clinical factors between LUAD and LUSC, and noted that patients with TMB≥10 and PD-L1≥50% exhibited enhanced immunotherapy effects. Combining TMB≥10 and PD-L1≥50% proved to be a more effective predictor of immunotherapy efficacy.