Testican 1 (SPOCK1) and protein tyrosine phosphatase, receptor type S (PTPRS) show significant increase in saliva of tobacco users with oral cancer

Author:

Nanjappa Vishalakshi12,Raja Remya13,Radhakrishnan Aneesha1,Jain Ankit P14,Datta Keshava K1,Puttamallesh Vinuth N12,Solanki Hitendra S14,Chavan Sandip1,Patil Arun14,Renuse Santosh1,Jain Anu5,Mathew Don6,Thakur Reetu6,Guerrero-Preston Rafael78,Nair Bipin2,Routray Samapika910,Mohanty Neeta9,Gowda KB Linge11,Jadav Ritesh12,Ghosal Sushmita6,Kumar Rekha V13,Ramesha Chaluvarayaswamy14,Raghu Vijay C14,Mathur Premendu Prakash415,Prasad TS Keshava1216,Califano Joseph A717,Sidransky David7,Pal Arnab5,Ganesh Mandakulutur S18,Ray Jay Gopal12,Pandey Akhilesh192021,Gowda Harsha116,Chatterjee Aditi116

Affiliation:

1. Institute of Bioinformatics, Bangalore, Karnataka, India

2. Amrita School of Biotechnology, Amrita University, Kollam, Kerala, India

3. Manipal Academy of Higher Education, Manipal, Karnataka, India

4. School of Biotechnology, KIIT University, Bhubaneswar, Odisha, India

5. Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India

6. Department of Radiotherapy, Postgraduate Institute of Medical Education and Research, Chandigarh, India

7. Head and Neck Cancer Research Division, Otolaryngology Department, School of Medicine, The Johns Hopkins University, Baltimore, USA

8. Department of Obstetrics and Gynecology, University of Puerto Rico School of Medicine, San Juan, Puerto Rico, USA

9. Department of Oral Pathology and Microbiology, Institute of Dental Sciences, Siksha’O’Anusandhan University, Bhubaneswar, Odisha, India

10. Department of Dental Surgery, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India

11. Department of Anesthetic and Pain Relief, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India

12. Deparment of Oral Pathology, Dr. R. Ahmed Dental College & Hospital, Kolkata, West Bengal, India

13. Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India

14. Department of Epidemiology and Biostatistics, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, India

15. Department of Biochemistry and Molecular Biology, Pondicherry University, Pondicherry, India

16. YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore, Karnataka, India

17. Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, Moores Cancer Center, University of California, San Diego, California, USA

18. Department of Surgical Oncology, Vydehi Institute of Oncology, Bangalore, Karnataka, India

19. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

20. Departments of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

21. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

Abstract

Objectives: To identify potential candidate proteins which are secretory in nature and present at a higher abundance in oral cancer patients with tobacco habits. Methods: Conditioned media of tobacco-treated and -untreated non-neoplastic oral keratinocytes were analyzed using iTRAQ-based mass spectrometry. Hypersecreted proteins; SPARC (osteonectin), cwcv and kazal like domains proteoglycan 1 (SPOCK1); prosaposin (PSAP); and protein tyrosine phosphatase, receptor type S (PTPRS) were validated by enzyme-linked immunosorbent assay (ELISA) using saliva samples from oral cancer patients who are tobacco users. Results: Proteomic analysis of tobacco-treated and -untreated cells led to the identification of 2873 proteins. Among these, 378 proteins showed high abundance and 253 proteins showed low abundance (2-fold cutoff) in conditioned-media of tobacco-treated cells. ELISA-based validation showed significantly higher levels of SPOCK1, PSAP, and PTPRS in oral cancer patients with tobacco chewing habits compared to healthy controls. However, PSAP showed low specificity compared to SPOCK1 and PTPRS. Conclusions: This study indicates significantly increased levels of SPOCK1, PSAP, and PTPRS in saliva of oral cancer patients with tobacco habits. These protein biomarkers might be useful to identify tobacco users with high risk of developing oral cancers.

Publisher

SAGE Publications

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