Differential Effect of Smoking on Gene Expression in Head and Neck Cancer Patients.

Alexandra Irimie,Lorand Magdo,Smaranda Buduru,Cornelia Braicu,Ioana Berindan-Neagoe,Roxana Cojocneanu,Anca Onaciu,Cristina Ciocan,Nikolay Mehterov,Diana Dudea

doi:10.3390/ijerph15071558

Abstract

Smoking is a well-known behavior that has an important negative impact on human health, and is considered to be a significant factor related to the development and progression of head and neck squamous cell carcinomas (HNSCCs). Use of high-dimensional datasets to discern novel HNSCC driver genes related to smoking represents an important challenge. The Cancer Genome Atlas (TCGA) analysis was performed in three co-existing groups of HNSCC in order to assess whether gene expression landscape is affected by tobacco smoking, having quit, or non-smoking status. We identified a set of differentially expressed genes that discriminate between smokers and non-smokers or based on human papilloma virus (HPV)16 status, or the co-occurrence of these two exposome components in HNSCC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways classification shows that most of the genes are specific to cellular metabolism, emphasizing metabolic detoxification pathways, metabolism of chemical carcinogenesis, or drug metabolism. In the case of HPV16-positive patients it has been demonstrated that the altered genes are related to cellular adhesion and inflammation. The correlation between smoking and the survival rate was not statistically significant. This emphasizes the importance of the complex environmental exposure and genetic factors in order to establish prevention assays and personalized care system for HNSCC, with the potential for being extended to other cancer types.

Highlights

Head and neck squamous cell carcinomas (HNSCCs) represent a preventable pathology which continues to be an important factor of morbidity with high mortality rates at global level [1,2], with over600,000 new cases detected each year [3,4], and a mortality rate of around 50% [5]
Global gene expression was evaluated in tumor tissues (n = 519) versus normal tissues (n = 43), where we identified 1216 upregulated genes and 1751 downregulated genes considering as cut-off the fold change (FC) value of ±2 and p-value ≤0.001 (Benjamini–Hochberg correction)
Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) classification, most of the upregulated genes belong to the extracellular matrix ECM–receptor interaction, focal adhesion, the PI3K (Phosphoinositide 3-kinase) –Akt (Protein kinase B) signaling pathway, or cell cycle regulation, while downregulated genes are involved in altered pathways belonging to drug metabolism cytochrome P450, chemical carcinogenesis and metabolism of xenobiotic by cytochrome P450

Summary

Introduction

Head and neck squamous cell carcinomas (HNSCCs) represent a preventable pathology which continues to be an important factor of morbidity with high mortality rates at global level [1,2], with over600,000 new cases detected each year [3,4], and a mortality rate of around 50% [5]. Head and neck squamous cell carcinomas (HNSCCs) represent a preventable pathology which continues to be an important factor of morbidity with high mortality rates at global level [1,2], with over. An important aspect in prevention and treatment is related to genetic and environmental components [2,7,8]. While the acquired genetic factors cannot be controlled in their early steps of mutation accumulation, environmental exposure can significantly affect the pathogenesis and the prognosis of these patients [8,9]. The totality of risk factors are integrated into the exposome [12], this being an important step in the evaluation of internal and external exposure, generally related to the co-occurrence of multiple toxic environmental agents [13]. The effect of co-occurrence is much more dramatic than that of the single exposure [13]

Methods

Results

Discussion

Conclusion