A novel prognostic biomarker combining TP53 loss‑of‑function and amplification of different combinations of nine genes in lung squamous cell carcinoma treated with chemotherapy

Lung squamous cell carcinoma (LUSC) is a prevalent subtype of lung cancer, which is primarily characterized by poor prognosis due to the lack of targeted therapies, while a large proportion of patients show limited response to chemotherapy. The present study aimed to identify predictive chemotherapy biomarkers based on genomic alterations in LUSC. Non‑negative matrix factorization clustering was applied to classify patients with LUSC into distinct subgroups based on genomic alterations. Subsequently, chemotherapy efficacy was predicted via exploring gene signatures, and the results were validated using The Cancer Genome Atlas database (TCGA). A total of four distinct clusters were classified. Cluster 1 and TP53 loss‑of‑function (TP53 LOF) variations were each independently associated with poor prognosis, irrespective of clinical stage. Based on the molecular characteristics of the initial clusters, the classification was further refined by further incorporating TP53 LOF and gene amplification (amp). Patients without TP53 LOF, who harbored amplification of at least one of nine specified genes [PIK3 catalytic subunit, cyclin D1, fibroblast growth factor (FGF) 19, FGF3, FGF4, FGF receptor 1, kinase insert domain receptor, KIT proto‑oncogene and platelet derived growth factor receptor α] displayed the longest progression‑free survival (PFS). By contrast, patients with TP53 LOF but lacking amplification of at least one of nine genes [Amp(9G)] exhibited the worst overall survival compared with the other subgroups. Validation in the TCGA database confirmed the prognostic significance of this classification, with Amp(9G) without TP53 LOF predicting the most favorable PFS, and TP53 LOF without Amp(9G) indicating the least favorable PFS. Therefore, a composite biomarker integrating Amp(9G) and TP53 LOF was identified as a prognostic indicator for patients with LUSC treated with first‑line chemotherapy. Overall, the results of the present study suggest that the absence of TP53 LOF combined with the presence of Amp(9G) could be associated with improved response to first‑line chemotherapy in LUSC.