title: Identification of head and neck squamous cell carcinoma biomarker candidates through proteomic analysis of cancer cell secretome.
abstract: Protein biomarker discovery for early detection of head and neck squamous cell carcinoma (HNSCC) is a crucial unmet need to improve patient outcomes. Mass spectrometry-based proteomics has emerged as a promising tool for identification of biomarkers in different cancer types. Proteins secreted from cancer cells can serve as potential biomarkers for early diagnosis. In the current study, we have used isobaric tag for relative and absolute quantitation (iTRAQ) labeling methodology coupled with high resolution mass spectrometry to identify and quantitate secreted proteins from a panel of head and neck carcinoma cell lines. In all, we identified 2,472 proteins, of which 225 proteins were secreted at higher or lower abundance in HNSCC-derived cell lines. Of these, 148 were present in higher abundance and 77 were present in lower abundance in the cancer-cell derived secretome. We detected a higher abundance of some previously known markers for HNSCC including insulin like growth factor binding protein 3, IGFBP3 (11-fold) and opioid growth factor receptor, OGFR (10-fold) demonstrating the validity of our approach. We also identified several novel secreted proteins in HNSCC including olfactomedin-4, OLFM4 (12-fold) and hepatocyte growth factor activator, HGFA (5-fold). IHC-based validation was conducted in HNSCC using tissue microarrays which revealed overexpression of IGFBP3 and OLFM4 in 70% and 75% of the tested cases, respectively. Our study illustrates quantitative proteomics of secretome as a robust approach for identification of potential HNSCC biomarkers. This article is part of a Special Issue entitled: An Updated Secretome.
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
authors.forename: Arivusudar
authors.initials: A
authors.lastname: Marimuthu
authors.forename: Sandip
authors.initials: S
authors.lastname: Chavan
authors.forename: Gajanan
authors.initials: G
authors.lastname: Sathe
authors.forename: Nandini A
authors.initials: NA
authors.lastname: Sahasrabuddhe
authors.forename: Srinivas M
authors.initials: SM
authors.lastname: Srikanth
authors.forename: Santosh
authors.initials: S
authors.lastname: Renuse
authors.forename: Sartaj
authors.initials: S
authors.lastname: Ahmad
authors.forename: Aneesha
authors.initials: A
authors.lastname: Radhakrishnan
authors.forename: Mustafa A
authors.initials: MA
authors.lastname: Barbhuiya
authors.forename: Rekha V
authors.initials: RV
authors.lastname: Kumar
authors.forename: H C
authors.initials: HC
authors.lastname: Harsha
authors.forename: David
authors.initials: D
authors.lastname: Sidransky
authors.forename: Joseph
authors.initials: J
authors.lastname: Califano
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
authors.forename: Aditi
authors.initials: A
authors.lastname: Chatterjee
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D006257:Head / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D009333:Neck / Q000473:pathology; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D055571:Secretory Pathway; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome
keywords: Body fluids; In vitro labeling; Oral carcinoma