Mutation Profiling Reveals Therapeutic Targets in Lung Squamous Cell Carcinoma

Background and objectives

Lung Squamous cell carcinoma (LSCC) represents the second most common non-small cell lung cancer. Although studies identified adenocarcinoma-like driver mutations in LSCC using next-generation sequencing (NGS), the disease is challenging to treat due to the limited number of detectable mutations for targeted drug therapy. This study aimed to evaluate the mutation profiles of LSCC detected by NGS to assess the relationships between different driver mutations and clinicopathological parameters.

Methods

NGS with a panel of 72 cancer-related genes was used to evaluate the driver mutation profiles of 41 lung resection specimens from patients with LSCC at the Molecular Pathology Laboratory of Aydın Adnan Menderes University in Türkiye. Clinical and histopathological features were recorded for analysis.

Results

Detection of 94 mutations in 23 genes in DNA extracted from the tissue samples of 36 patients revealed that the most prevalent mutations were TP53 (30.85%), NF1 (20.20%), PTEN (11.70%), PIK3CA (5.31%), FBXW7 (4.25%), KRAS (3.20%), respectively. We identified statistically significant relationships between PIK3CA and lower mean age (p = 0.007) and between PTEN and mild inflammatory reaction (p = 0.004). PTEN was associated with central localization (p = 0.13), NF1 with visceral pleural involvement (p = 0.09), and PIK3CA with severe inflammatory reaction (p = 0.053), as well as with advanced pathological T stage (p = 0.09) and pathological N stage (p = 0.057) according to the TNM staging system.

Conclusions

In the era of personalized medicine, treatment for LSCC lags behind that for LADC, but new developments in this field. Careful selection of therapeutic targets is essential, as grouping multiple alterations together may lead to the oversight of true driver mutations. Similarly, drug selection and potential combinations will play a crucial role In treatment efficacy. Promising studies, including ours, will enhance understanding of the clinical relevance of suspected driver mutations. Our study identified novel mutations and their relationships, such as NF1, PTEN, and PIK3CA, which have not been previously reported in LSCC and may have significant therapeutic and prognostic implications. Given the molecular heterogeneity observed in LSCC, it is imperative to ascertain the mutational profile in all LSCC patients to identify driver mutations that are amenable to targeted therapy. Our data suggest that certain histopathological features may be associated with mutations, providing reliable information to enhance treatment and follow-up decisions.