Molecular and immune predictors of survival in lung squamous cell carcinoma: A TCGA-based analysis
DOI:
https://doi.org/10.63341/bmbr/3.2025.26Keywords:
TP53, TTN, PIK3CA, KEAP1/NFE2L2, lung cancer, co-mutationsAbstract
Lung squamous cell carcinoma remains one of the most aggressive forms of non-small cell lung cancer with limited options for personalised therapy, highlighting the need for new prognostic biomarkers. The purpose of this study was to analyse the impact of somatic mutations and their co-mutations in key oncogenes (TP53, TTN, PIK3CA, and KEAP1/NFE2L2) on the survival of patients with lung squamous cell carcinoma, considering the tumour immune subtype. Data from open-access oncology repositories (TCGA, UCSC Xena, cBioPortal) were used for 419 patients with complete clinical, immune, and mutational profiles. Patients were stratified by tumour immune activity (high/intermediate vs low subtype), and the mutational analysis included both individual genes and co-mutations. Survival was assessed using the Kaplan-Meier method with log-rank testing. It was found that TP53 mutations were significantly associated with improved survival in both the high/intermediate immune subtype group (median 57.9 vs 27.8 months, p = 0.0141) and the low immune subtype group (p = 0.0361). TTN mutations showed a positive trend in the high/intermediate group (p = 0.0582) and a statistically significant association with survival in the low immune activity group (p=0.0123). The strongest effect was observed for the TP53+TTN co-mutation, which significantly improved survival in both immune subtypes (high/ intermediate: p= 0.0065; low: p= 0.0006). In contrast, PIK3CA and KEAP1/NFE2L2 mutations and their combinations did not show a statistically significant impact on survival. Cluster analysis of the mutational profile revealed two primary patterns, with TP53 and TTN mutations tending to cluster, though no clear visual association with survival status was observed. Thus, the mutational status of TP53 and TTN, particularly their co-mutation, has substantial prognostic value in patients with lung squamous cell carcinoma, especially when considered alongside immune microenvironment characteristics. Isolated PIK3CA and KEAP1/NFE2L2 mutations showed no significant effect. These results emphasised the importance of integrating mutational and immune profiling to guide personalised treatment strategies
Received: 30.04.2025 | Revised: 31.07.2025 | Accepted: 02.09.2025
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