Expression of S100A2 Calcium-Binding Protein Predicts Response to Pancreatectomy for Pancreatic Cancer

Biankin, AV; Kench, JG; Colvin, EK; Segara, D; Scarlett, CJ; Nguyen, NQ; Chang, DK; Morey, AL; Lee, CS; Pinese, M; Kuo, SCL; Susanto, JM; Cosman, PH; Lindeman, GJ; Visvader, JE; Nguyen, TV; Merrett, ND; Warusavitarne, J; Musgrove, EA; Henshall, SM; Sutherland, RL

Expression of S100A2 Calcium-Binding Protein Predicts Response to Pancreatectomy for Pancreatic Cancer

Biankin, AV Kench, JG Colvin, EK Segara, D Scarlett, CJ Nguyen, NQ Chang, DK Morey, AL Lee, CS Pinese, M Kuo, SCL Susanto, JM Cosman, PH Lindeman, GJ Visvader, JE Nguyen, TV

Merrett, ND Warusavitarne, J Musgrove, EA Henshall, SM Sutherland, RL

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Publication Type:: Journal Article
Citation:: Gastroenterology, 2009, 137 (2)
Issue Date:: 2009-01-01

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Field	Value	Language
dc.contributor.author	Biankin, AV	en_US
dc.contributor.author	Kench, JG	en_US
dc.contributor.author	Colvin, EK	en_US
dc.contributor.author	Segara, D	en_US
dc.contributor.author	Scarlett, CJ	en_US
dc.contributor.author	Nguyen, NQ	en_US
dc.contributor.author	Chang, DK	en_US
dc.contributor.author	Morey, AL	en_US
dc.contributor.author	Lee, CS	en_US
dc.contributor.author	Pinese, M	en_US
dc.contributor.author	Kuo, SCL	en_US
dc.contributor.author	Susanto, JM	en_US
dc.contributor.author	Cosman, PH	en_US
dc.contributor.author	Lindeman, GJ	en_US
dc.contributor.author	Visvader, JE	en_US
dc.contributor.author	Nguyen, TV https://orcid.org/0000-0002-3246-6281	en_US
dc.contributor.author	Merrett, ND	en_US
dc.contributor.author	Warusavitarne, J	en_US
dc.contributor.author	Musgrove, EA	en_US
dc.contributor.author	Henshall, SM	en_US
dc.contributor.author	Sutherland, RL	en_US
dc.date.available	2009-04-09	en_US
dc.date.issued	2009-01-01	en_US
dc.identifier.citation	Gastroenterology, 2009, 137 (2)	en_US
dc.identifier.issn	0016-5085	en_US
dc.identifier.uri	http://hdl.handle.net/10453/28794
dc.description.abstract	Background & Aims: Current methods of preoperative staging and predicting outcome following pancreatectomy for pancreatic cancer (PC) are inadequate. We evaluated the utility of multiple biomarkers from distinct biologic pathways as potential predictive markers of response to pancreatectomy and patient survival. Methods: We assessed the relationship of candidate biomarkers known, or suspected, to be aberrantly expressed in PC, with disease-specific survival and response to therapy in a cohort of 601 patients. Results: Of the 17 candidate biomarkers examined, only elevated expression of S100A2 was an independent predictor of survival in both the training (n = 162) and validation sets (n = 439; hazard ratio [HR], 2.19; 95% confidence interval [CI]: 1.48-3.25; P < .0001) when assessed in a multivariate model with clinical variables. Patients with high S100A2 expressing tumors had no survival benefit with pancreatectomy compared with those with locally advanced disease, whereas those without high S100A2 expression had a survival advantage of 10.6 months (19.4 vs 8.8 months, respectively) and a HR of 3.23 (95% CI: 2.39-4.33; P < .0001). Of significance, patients with S100A2-negative tumors had a significant survival benefit from pancreatectomy even in the presence of involved surgical margins (median, 15.7 months; P = .0007) or lymph node metastases (median, 17.4 months; P = .0002). Conclusions: S100A2 expression is a good predictor of response to pancreatectomy for PC and suggests that high S100A2 expression may be a marker of a metastatic phenotype. Prospective measurement of S100A2 expression in diagnostic biopsy samples has potential clinical utility as a predictive marker of response to pancreatectomy and other therapies that target locoregional disease. © 2009 AGA Institute.	en_US
dc.relation.ispartof	Gastroenterology	en_US
dc.relation.isbasedon	10.1053/j.gastro.2009.04.009	en_US
dc.subject.classification	Gastroenterology & Hepatology	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Adenocarcinoma	en_US
dc.subject.mesh	Pancreatic Neoplasms	en_US
dc.subject.mesh	Postoperative Complications	en_US
dc.subject.mesh	S100 Proteins	en_US
dc.subject.mesh	Tumor Markers, Biological	en_US
dc.subject.mesh	Neoplasm Staging	en_US
dc.subject.mesh	Disease-Free Survival	en_US
dc.subject.mesh	Treatment Outcome	en_US
dc.subject.mesh	Pancreatectomy	en_US
dc.subject.mesh	Survival Rate	en_US
dc.subject.mesh	Confidence Intervals	en_US
dc.subject.mesh	Proportional Hazards Models	en_US
dc.subject.mesh	Probability	en_US
dc.subject.mesh	Risk Assessment	en_US
dc.subject.mesh	Sensitivity and Specificity	en_US
dc.subject.mesh	Cohort Studies	en_US
dc.subject.mesh	Follow-Up Studies	en_US
dc.subject.mesh	Predictive Value of Tests	en_US
dc.subject.mesh	Gene Expression Regulation, Neoplastic	en_US
dc.subject.mesh	Time Factors	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Aged	en_US
dc.subject.mesh	Aged, 80 and over	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Kaplan-Meier Estimate	en_US
dc.subject.mesh	Biomarkers, Tumor	en_US
dc.title	Expression of S100A2 Calcium-Binding Protein Predicts Response to Pancreatectomy for Pancreatic Cancer	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	137	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	1109 Neurosciences	en_US
utslib.for	1114 Paediatrics and Reproductive Medicine	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	closed_access
pubs.issue	2	en_US
pubs.publication-status	Published	en_US
pubs.volume	137	en_US

Abstract:

Background & Aims: Current methods of preoperative staging and predicting outcome following pancreatectomy for pancreatic cancer (PC) are inadequate. We evaluated the utility of multiple biomarkers from distinct biologic pathways as potential predictive markers of response to pancreatectomy and patient survival. Methods: We assessed the relationship of candidate biomarkers known, or suspected, to be aberrantly expressed in PC, with disease-specific survival and response to therapy in a cohort of 601 patients. Results: Of the 17 candidate biomarkers examined, only elevated expression of S100A2 was an independent predictor of survival in both the training (n = 162) and validation sets (n = 439; hazard ratio [HR], 2.19; 95% confidence interval [CI]: 1.48-3.25; P < .0001) when assessed in a multivariate model with clinical variables. Patients with high S100A2 expressing tumors had no survival benefit with pancreatectomy compared with those with locally advanced disease, whereas those without high S100A2 expression had a survival advantage of 10.6 months (19.4 vs 8.8 months, respectively) and a HR of 3.23 (95% CI: 2.39-4.33; P < .0001). Of significance, patients with S100A2-negative tumors had a significant survival benefit from pancreatectomy even in the presence of involved surgical margins (median, 15.7 months; P = .0007) or lymph node metastases (median, 17.4 months; P = .0002). Conclusions: S100A2 expression is a good predictor of response to pancreatectomy for PC and suggests that high S100A2 expression may be a marker of a metastatic phenotype. Prospective measurement of S100A2 expression in diagnostic biopsy samples has potential clinical utility as a predictive marker of response to pancreatectomy and other therapies that target locoregional disease. © 2009 AGA Institute.

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http://hdl.handle.net/10453/28794