Molecular alterations in oral cancer between tobacco chewers and smokers using serum proteomics

Article type: Research Article

Authors: Mohanty, Varshasnata^{a; 1} | Subbannayya, Yashwanth^{a; b; 1} | Patil, Shankargouda^c | Abdulla, Riaz^d | Ganesh, Mandakulutur S.^e | Pal, Arnab^f | Ray, Jay Gopal^{g; k} | Sidransky, David^h | Gowda, Harsha^{a; i; j} | Prasad, T.S. Keshava^{a; *} | Chatterjee, Aditi^{a; i; j; *}

Affiliations: [a] Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to be University), Mangalore, Karnataka, India | [b] Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, Trondheim, Norway | [c] Division of Oral Pathology, College of Dentistry, Department of Maxillofacial Surgery and Diagnostic Sciences, Jazan University, Jazan, Saudi Arabia | [d] Department of Oral Pathology, Yenepoya Dental College, Yenepoya (Deemed to be University), Mangalore, Karnataka, India | [e] Department of Surgical Oncology, Vydehi Institute of Oncology, Bangalore, Karnataka, India | [f] Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India | [g] Department of Oral Pathology, Dr. R Ahmed Dental College and Hospital, Kolkata, West Bengal, India | [h] Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, School of Medicine, Baltimore, MD, USA | [i] Institute of Bioinformatics, International Tech Park, Bangalore, Karnataka, India | [j] Manipal Academy of Higher Education, Manipal, Karnataka, India | [k] Department of Pathology, Burdwan Dental College and Hospital, Burdwan, West Bengal, India

Correspondence: [*] Corresponding authors: T.S. Keshava Prasad and Aditi Chatterjee, Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore 575018, India. Tel.: +91 9972250102 and +91 9591100113; E-mail: [email protected]@gmail.com.

Note: [1] These authors contributed equally to the manuscript.

Abstract: BACKGROUND: Tobacco exposure (through smoking or chewing) is one of the predominant risk factors associated with the development of oral squamous cell carcinoma (OSCC). Despite the growing number of patients diagnosed with OSCC, there are few circulating biomarkers for identifying individuals at a higher risk of developing the disease. Successful identification of candidate molecular markers for risk assessment could aid in the early detection of oral lesions and potentially be used for community screening of high-risk populations. OBJECTIVE: Identification of differentially expressed proteins in the serum of oral cancer patients which can serve as biomarkers for the diagnosis of the onset of oral cancer among tobacco users. METHODS: We employed a tandem mass tag (TMT)-based quantitative proteomics approach to study alterations in the serum proteomes of OSCC patients based on their tobacco exposure habits (chewing and smoking) compared to healthy individuals with no history of using any form of tobacco or any symptoms of the disease. RESULTS: Mass spectrometry-based analysis resulted in the identification of distinct signatures in the serum of OSCC patients who either chewed or smoked tobacco. Pathway analysis revealed opposing effects of dysregulated proteins enriched in the complement-coagulation signaling cascades with a high expression of the Serpin family of proteins observed in OSCC patients who chewed tobacco compared to healthy individuals whereas these proteins showed decreased levels in OSCC patients who smoked. ELISA-based validation further confirmed our findings revealing higher expression of SERPINA6 and SERPINF1 across serum of OSCC patients who chewed tobacco compared to healthy individuals. CONCLUSIONS: This study serves as a benchmark for the identification of serum-based protein markers that may aid in the identification of high-risk patients who either chew tobacco or smoke tobacco.

Keywords: Oral cancer, squamous cell carcinoma, tobacco, mass spectrometry, serum proteomics, cigarette smoke

DOI: 10.3233/CBM-203077

Journal: Cancer Biomarkers, vol. 31, no. 4, pp. 361-373, 2021