title: S100A7 overexpression is a predictive marker for high risk of malignant transformation in oral dysplasia.
abstract: Early detection of oral lesions (OLs) at high risk of cancer development is of utmost importance for intervention. There is an urgent unmet clinical need for biomarkers that allow identification of high-risk OLs. Recently, we identified and verified a panel of five candidate protein biomarkers namely S100A7, prothymosin alpha, 14-3-3ζ, 14-3-3σ and heterogeneous nuclear ribonucleoprotein K using proteomics to distinguish OLs with dysplasia and oral cancers from normal oral tissues. The objective of our study was to evaluate the potential of these candidate protein biomarkers for identification of oral dysplastic lesions at high risk of cancer development. Using immunohistochemistry, we analyzed expressions of these five candidate protein biomarkers in 110 patients with biopsy-proven oral dysplasia and known clinical outcome and determined their correlations with p16 expression and HPV 16/18 status. Kaplan-Meier survival analysis showed reduced oral cancer-free survival (OCFS) of 68.6 months (p = 0.007) in patients showing cytoplasmic S100A7 overexpression when compared to patients with weak or no S100A7 immunostaining in cytoplasm (mean OCFS = 122.8 months). Multivariate Cox regression analysis revealed cytoplasmic S100A7 overexpression as the most significant candidate marker associated with cancer development in dysplastic lesions (p = 0.041, hazard ratio = 2.36). In conclusion, our study suggested the potential of S100A7 overexpression in identifying OLs with dysplasia at high risk of cancer development.
authors.affiliation: Alex and Simona Shnaider Laboratory in Molecular Oncology, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, Toronto, ON, Canada.
authors.forename: Jatinder
authors.initials: J
authors.lastname: Kaur
authors.forename: Ajay
authors.initials: A
authors.lastname: Matta
authors.forename: Ipshita
authors.initials: I
authors.lastname: Kak
authors.forename: Gunjan
authors.initials: G
authors.lastname: Srivastava
authors.forename: Jasmeet
authors.initials: J
authors.lastname: Assi
authors.forename: Iona
authors.initials: I
authors.lastname: Leong
authors.forename: Ian
authors.initials: I
authors.lastname: Witterick
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Colgan
authors.forename: Christina
authors.initials: C
authors.lastname: Macmillan
authors.forename: K W Michael
authors.initials: KW
authors.lastname: Siu
authors.forename: Paul G
authors.initials: PG
authors.lastname: Walfish
authors.forename: Ranju
authors.initials: R
authors.lastname: Ralhan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007972:Leukoplakia, Oral / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human
keywords: 14-3-3ζ; 14-3-3σ; PTMA; S100A7; biomarker; dysplasia; hnRNPK; immunohistochemistry; oral cancer; progression; transformation