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Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients

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 translat...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324434/
https://www.ncbi.nlm.nih.gov/pubmed/25591983
http://dx.doi.org/10.1186/s12967-014-0369-9
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author 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
author_facet 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
author_sort Kumar, Manish
collection PubMed
description 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.
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spelling pubmed-43244342015-02-12 Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients 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 J Transl Med Research 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. BioMed Central 2015-01-16 /pmc/articles/PMC4324434/ /pubmed/25591983 http://dx.doi.org/10.1186/s12967-014-0369-9 Text en © Kumar et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
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
Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients
title Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients
title_full Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients
title_fullStr Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients
title_full_unstemmed Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients
title_short Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients
title_sort prognostic significance of cytoplasmic s100a2 overexpression in oral cancer patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324434/
https://www.ncbi.nlm.nih.gov/pubmed/25591983
http://dx.doi.org/10.1186/s12967-014-0369-9
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