title: Nuclear S100A7 is associated with poor prognosis in head and neck cancer.
abstract: BACKGROUND
  Tissue proteomic analysis of head and neck squamous cell carcinoma (HNSCC) and normal oral mucosa using iTRAQ (isobaric tag for relative and absolute quantitation) labeling and liquid chromatography-mass spectrometry, led to the identification of a panel of biomarkers including S100A7. In the multi-step process of head and neck tumorigenesis, the presence of dysplastic areas in the epithelium is proposed to be associated with a likely progression to cancer; however there are no established biomarkers to predict their potential of malignant transformation. This study aimed to determine the clinical significance of S100A7 overexpression in HNSCC.
  
  
  METHODS
  Immunohistochemical analysis of S100A7 expression in HNSCC (100 cases), oral lesions (166 cases) and 100 histologically normal tissues was carried out and correlated with clinicopathological parameters and disease prognosis over 7 years for HNSCC patients. Overexpression of S100A7 protein was significant in oral lesions (squamous cell hyperplasia/dysplasia) and sustained in HNSCC in comparison with oral normal mucosa (p(trend)<0.001). Significant increase in nuclear S100A7 was observed in HNSCC as compared to dysplastic lesions (p = 0.005) and associated with well differentiated squamous cell carcinoma (p = 0.031). Notably, nuclear accumulation of S100A7 also emerged as an independent predictor of reduced disease free survival (p = 0.006, Hazard ratio (HR = 7.6), 95% CI = 1.3-5.1) in multivariate analysis underscoring its relevance as a poor prognosticator of HNSCC patients.
  
  
  CONCLUSIONS
  Our study demonstrated nuclear accumulation of S100A7 may serve as predictor of poor prognosis in HNSCC patients. Further, increased nuclear accumulation of S100A7 in HNSCC as compared to dysplastic lesions warrants a large-scale longitudinal study of patients with dysplasia to evaluate its potential as a determinant of increased risk of transformation of oral premalignant lesions.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Satyendra Chandra
authors.initials: SC
authors.lastname: Tripathi
authors.forename: Ajay
authors.initials: A
authors.lastname: Matta
authors.forename: Jatinder
authors.initials: J
authors.lastname: Kaur
authors.forename: Jorg
authors.initials: J
authors.lastname: Grigull
authors.forename: Shyam Singh
authors.initials: SS
authors.lastname: Chauhan
authors.forename: Alok
authors.initials: A
authors.lastname: Thakar
authors.forename: Nootan Kumar
authors.initials: NK
authors.lastname: Shukla
authors.forename: Ritu
authors.initials: R
authors.lastname: Duggal
authors.forename: Siddhartha
authors.initials: S
authors.lastname: DattaGupta
authors.forename: Ranju
authors.initials: R
authors.lastname: Ralhan
authors.forename: K W Michael
authors.initials: KW
authors.lastname: Siu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007972:Leukoplakia, Oral / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human