Introduction: Platinum-based chemotherapy is the cornerstone of treatment for patients with LUSC, but cisplatin resistance greatly restricts its clinical application. Therefore, it is particularly important to screen the predominant LUSC population using biomarkers.
Methods: Data for 15 LUSC cell lines were downloaded from the Genomics of Drug Sensitivity in Cancer (GDSC) Project database to screen for mutations related to cisplatin susceptibility. We conducted whole-exome sequencing (WES) of tumors from 58 LUSC patients from Sichuan Provincial People’s Hospital of University of Electronic Science and Technology. Subsequently, the clinical prognostic value of these mutations was verified by using The Cancer Genome Atlas (TCGA)-LUSC cohort and our cohort (n=58).
Results: Based on the cisplatin sensitivity data of GDSC-LUSC and survival analysis of TCGA-LUSC and Local-LUSC cohorts, we found that only mutation of IGF2R was associated with cisplatin sensitivity, better overall survival [OS; P=0.04, HR (95% CI): 0.42 (0.23– 0.78)] and progression-free survival [PFS; P =0.016, HR (95% CI): 0.26 (0.12– 0.59)]. However, there were no significant differences in the frequencies of gene mutations between the IGF2R-mutant (IGF2R-MT) and IGF2R-wild-type (IGF2R-WT) groups. Gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) indicated enhanced intracellular detoxification and decreased abnormal signaling activity to reverse cisplatin tolerance in the IGF2R-MT group.
Conclusion: The results suggest that IGF2R mutations are a potential biomarker for screening LUSC patients suitable for cisplatin treatment.
Keywords: cisplatin, lung squamous cell carcinoma, resistance, mutation, chemotherapy