Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients

• Published in: Journal of translational medicine 2015-01, Vol.13 (1), p.8-8, Article 8
• Main Authors: Kumar, Manish, Srivastava, Gunjan, Kaur, Jatinder, Assi, Jasmeet, Alyass, Akram, Leong, Iona, MacMillan, Christina, Witterick, Ian, Shukla, Nootan Kumar, Thakar, Alok, Duggal, Ritu, Roychoudhury, Ajoy, Sharma, Mehar Chand, Walfish, Paul G, Chauhan, Shyam Singh, Ralhan, Ranju
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Analysis; Canadian native peoples; Cancer; Cancer patients; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Care and treatment; Chemotactic Factors - metabolism; Cytoplasm - metabolism; Diseases; Female; Health aspects; Humans; Immunohistochemistry; Male; Middle Aged; Mouth cancer; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Oncology, Experimental; Prognosis; Proportional Hazards Models; Protein binding; Relapse; S100 Proteins - metabolism; Squamous cell carcinoma; Time Factors; Young Adult
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-014-0369-9

Oral squamous cell carcinoma (OSCC) patients are at high risk of loco-regional recurrence and 5-year survival rates are about 50%. Identification of patients at high risk of recurrence will enable rigorous personalized post-treatment management. Most novel biomarkers have failed translation for clinical use because of their limited successful validation in external patient cohorts. The aim of this study was to determine the prognostic significance of alterations in sub-cellular expression of S100A2, a pro-tumorigenic calcium binding protein, identified as a candidate biomarker in our proteomic analysis in OSCC and validation of its clinical utility in an external cohort. In a retrospective study, immunohistochemical analysis of S100A2 was carried out in 235 Indian OSCC (Test set) and 129 normal oral tissues, correlated with clinicopathological parameters and disease outcome over 122 months for OSCC patients following the REMARK criteria. The findings were validated in an external cohort (Validation set 115 Canadian OSCC and 51 normal tissues) and data analyzed using the R package. Significant increase in cytoplasmic and decrease in nuclear S100A2 expression was observed in OSCC in comparison with normal tissues. Cox multivariable regression analysis internally and externally validated cytoplasmic S100A2 association with tumor recurrence. Kaplan Meier analysis of patients stratified to high and low risk groups showed significantly different recurrence free survival (Test set- log rank test, p = 0.005, median survival 16 and 69 months respectively and Validation set - p