Proteomic Alterations Associated with Oral Cancer Patients with Tobacco Using Habits.

Firdous Ahmad Bhat,Harsha Gowda,Shankargouda Patil,Neeta Mohanty,Jayshree Advani,Mohd Younis Bhat,Samapika Routray,Sonali V Mohan,Jay Gopal Ray,David Sidransky,Krishna Patel,S Ganesh Mandakulutur,Aditi Chatterjee,Arnab Pal,Keshava K Datta,Bipin Nair,Kiran K Mangalaparthi

doi:10.1089/omi.2021.0001

Abstract

Tobacco abuse is a major risk factor associated with the development of oral squamous cell carcinoma. Differences in molecular aberrations induced by tobacco exposure by chewing or smoking form are not well studied in case of oral cancer. We used tandem mass tag-based quantitative proteomic approach to delineate proteomic alterations in oral cancer patients based on their history of tobacco using habits (patients who chewed tobacco, patients who smoked tobacco, and those with no history of tobacco consumption). Our data identified distinct dysregulation of biological processes and pathways in each patient cohort. Bioinformatics analysis of dysregulated proteins identified in our proteomic study revealed dysregulation of collagen formation and antigen processing/presentation pathway in oral cancer patients who smoked tobacco, whereas proteins associated with the process of keratinization showed enrichment in patients who chewed tobacco. In addition, we identified overexpression of proteins involved in immune pathways and downregulation of muscle contraction-mediated signaling events in all three cohorts, irrespective of tobacco using habits. This study lays the groundwork for identification of protein markers that may aid in identification of high-risk patients for cancer development based on the history of tobacco exposure habits.

Highlights

Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancers with tongue and buccal mucosa being the most reported affected sites (Rivera and Venegas, 2014)
To study proteomic alterations in OSCC patient tissue samples based on their tobacco usage history, three independent Tandem mass tag (TMT) 10plex experiments were carried out using samples from patients who smoked tobacco, patients who chewed tobacco, and patients with no history of tobacco consumption
We investigated the underlying molecular alterations in OSCC based on the history of tobacco intake

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is the most common form of head and neck cancers with tongue and buccal mucosa being the most reported affected sites (Rivera and Venegas, 2014). The major risk factors associated with development of oral cancer include chewing of tobacco and betel leaf, cigarette smoking, consumption of alcohol, and infection by human papilloma virus, mostly HPV-16 (Ram et al, 2011). Our group has demonstrated that chronic exposure to cigarette smoke and chewing tobacco to oral keratinocytes resulted in increased cell proliferation, migration, and invasion (Nanjappa et al, 2015; Rajagopalan et al, 2018). Smokeless tobacco was shown to dysregulate key metabolic pathways and promote angiogenesis and metastasis in esophageal and head and neck squamous cell carcinoma (Datta et al, 2019; Macha et al, 2011). Literature indicates that tobacco users are at higher risk of developing oral cancer compared with tobacco nonusers (Sadri and Mahjub, 2007). Scheidt et al (2013) have indicated significant differences in prognosis, aggressiveness of cancer, rate of recurrence, and response to treatment in OSCC patients based on tobacco using habits

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