Abstract
BackgroundWe aimed at identifying druggable molecular alterations at the RNA level from untreated HNSCC patients, and assessing their prognostic significance.MethodsWe retrieved 96 HNSCC patients who underwent primary surgery. Real-time quantitative RT-PCR was used to analyze a panel of 42 genes coding for major druggable proteins. Univariate and multivariate analyses were performed to assess the prognostic significance of overexpressed genes.ResultsMedian age was 56 years [35–78]. Most of patients were men (80%) with a history of alcohol (70.4%) and/or tobacco consumption (72.5%). Twelve patients (12%) were HPV-positive. Most significantly overexpressed genes involved cell cycle regulation (CCND1 [27%], CDK6 [21%]), tyrosine kinase receptors (MET [18%], EGFR [14%]), angiogenesis (PGF [301%], VEGFA [14%]), and immune system (PDL1/CD274 [28%]). PIK3CA expression was an independent prognostic marker, associated with shorter disease-free survival.ConclusionsWe identified druggable overexpressed genes associated with a poor outcome that might be of interest for personalizing treatment of HNSCC patients.
Highlights
Head and neck squamous cell carcinoma is the fifth most common cancer worldwide [1]
We identified druggable overexpressed genes associated with a poor outcome that might be of interest for personalizing treatment of HNSCC patients
Among the 42 genes analyzed, our study reveals that 6 are relevant targets in head and neck squamous cell carcinoma: PGF, PDL1/CD274, CDK6, EGFR, MET, VEGFA
Summary
Head and neck squamous cell carcinoma is the fifth most common cancer worldwide [1]. Multimodal management of non-metastatic disease includes surgery, radiotherapy, and chemotherapy. Prognosis of patients remains poor when they recur, with more than half of locally advanced HNSCC patients who recur [2, 3]. The Cancer Genome Atlas (TCGA) recently published the whole genome analysis of HNSCC, reporting DNA mutations, gene copy number alterations and main altered expressed genes [4]. That targets EGFR, is the only approved targeted agent in combination with radiotherapy for HNSCC treatment in the recurrent and/or metastatic setting [5, 6]. We aimed at identifying druggable molecular alterations at the RNA level from untreated HNSCC patients, and assessing their prognostic significance
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