Special transcriptome landscape and molecular prognostic signature of non-smoking head and neck cancer patients

Abstract

As a well-known behavioral risk factor for human health, smoking is involved in carcinogenesis, tumor progression, and therapeutic interventions of head and neck squamous cell carcinoma (HNSCC). The stratification of disease subtypes according to tobacco use is expressively needed for HNSCC precision therapy. High-throughput transcriptome profiling by RNA sequencing (RNA-seq) from The Cancer Genome Atlas (TCGA) was collected and collated for differential expression analysis and pathway enrichment analysis to characterize the molecular landscape for non-smoking HNSCC patients. Molecular prognostic signatures specific to non-smoking HNSCC patients were identified by the least absolute shrinkage and selection operator (LASSO) analysis and were then verified via internal and external validation cohorts. While proceeding to immune cell infiltration and after drug sensitivity analysis was further carried out, a proprietary nomogram was finally developed for their respective clinical applications. In what it relates to the non-smoking cohort, the enrichment analysis pointed to human papillomavirus (HPV) infection and PI3K-Akt signaling pathway, with the prognostic signature consisting of another ten prognostic genes (COL22A1, ADIPOQ, RAG1, GREM1, APBA2, SPINK9, SPP1, ARMC4, C6, and F2RL2). These signatures showed to be independent factors, and the related nomograms were, thus, constructed for their further and respective clinical applications. While the molecular landscapes and proprietary prognostic signature were characterized based on non-smoking HNSCC patients, a clinical nomogram was constructed to provide better HNSCC patient classification and guide treatment for non-smoking HNSCC patients. Nonetheless, there are still significant challenges in the recognition, diagnosis, treatment, and understanding of the potentially efficient mechanisms of HNSCC with no tobacco use.

Keywords: HNSCC; Non-smoking; Outcome; Prognosis; Smoking.