Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients

Journal of Translational Medicine

Ranju Ralhan⁷  Shyam Singh Chauhan⁶  Paul G Walfish⁷  Mehar Chand Sharma⁶  Ajoy Roychoudhury¹  Ritu Duggal¹  Alok Thakar³  Nootan Kumar Shukla⁴  Ian Witterick⁷  Christina MacMillan⁸  Iona Leong⁹  Akram Alyass⁵  Jasmeet Assi²  Jatinder Kaur⁶  Gunjan Srivastava²  Manish Kumar⁶ 

[1] Centre for Dental Education and Research, All India Institute of Medical Sciences, New Delhi, India;Alex and Simona Shnaider Laboratory of Molecular Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada;Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi, India;Department of Surgery, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India;Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada;Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India;Department of Otolaryngology – Head and Neck Surgery, University of Toronto, 190 Elizabeth Street, Toronto M5G 2N2, Ontario, Canada;Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Joseph & Wolf Lebovic Health Complex, 600 University Avenue, Toronto M5G 1X5, Ontario, Canada;Department of Oral Pathology and Oral Medicine, Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto M5G 1G6, Ontario, Canada

关键词: Prognosis;    Head-and-neck cancer;    Squamous cell carcinoma;    Dysplasia;    Squamous cell hyperplasia;    Oral lesion;    S100A2;   

Others  :  1146391
DOI  :  10.1186/s12967-014-0369-9

 received in 2014-09-17, accepted in 2014-12-18,  发布年份 2015

【 摘 要 】

Background

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.

Methods

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.

Results

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 < 0.00001, median survival 9.4 and 59.9 months respectively); 86% and 81% of patients who had recurrence were correctly stratified into the high risk group. Seventy percent and 81% patients stratified into low risk group did not show cancer recurrence within 1 year in Test and Validation sets.

Conclusions

Our study provided clinical evidence for the potential of cytoplasmic S100A2 overexpression as a predictor of recurrence risk in OSCC patients. A unique translational aspect of our study is validation of S100A2 as prognostic marker in two independent cohorts (Canadian and Indian) suggesting this protein is likely to find widespread utility in clinical practice for identifying oral cancer patients at high risk of disease recurrence.

【 授权许可】

   
2015 Kumar et al.; licensee BioMed Central.

【 图 表 】

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