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.
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.
Authors: Wilson Petrushnko; Justin S Gundara; Philip R De Reuver; Greg O'Grady; Jaswinder S Samra; Anubhav Mittal Journal: HPB (Oxford) Date: 2016-07-14 Impact factor: 3.647
Authors: Yi Zhong; Yoshiki Naito; Leslie Cope; Salvador Naranjo-Suarez; Tyler Saunders; Seung-Mo Hong; Michael G Goggins; Joseph M Herman; Christopher L Wolfgang; Christine A Iacobuzio-Donahue Journal: Clin Cancer Res Date: 2014-06-24 Impact factor: 12.531
Authors: Andrew V Biankin; Nicola Waddell; Karin S Kassahn; Marie-Claude Gingras; Lakshmi B Muthuswamy; Amber L Johns; David K Miller; Peter J Wilson; Ann-Marie Patch; Jianmin Wu; David K Chang; Mark J Cowley; Brooke B Gardiner; Sarah Song; Ivon Harliwong; Senel Idrisoglu; Craig Nourse; Ehsan Nourbakhsh; Suzanne Manning; Shivangi Wani; Milena Gongora; Marina Pajic; Christopher J Scarlett; Anthony J Gill; Andreia V Pinho; Ilse Rooman; Matthew Anderson; Oliver Holmes; Conrad Leonard; Darrin Taylor; Scott Wood; Qinying Xu; Katia Nones; J Lynn Fink; Angelika Christ; Tim Bruxner; Nicole Cloonan; Gabriel Kolle; Felicity Newell; Mark Pinese; R Scott Mead; Jeremy L Humphris; Warren Kaplan; Marc D Jones; Emily K Colvin; Adnan M Nagrial; Emily S Humphrey; Angela Chou; Venessa T Chin; Lorraine A Chantrill; Amanda Mawson; Jaswinder S Samra; James G Kench; Jessica A Lovell; Roger J Daly; Neil D Merrett; Christopher Toon; Krishna Epari; Nam Q Nguyen; Andrew Barbour; Nikolajs Zeps; Nipun Kakkar; Fengmei Zhao; Yuan Qing Wu; Min Wang; Donna M Muzny; William E Fisher; F Charles Brunicardi; Sally E Hodges; Jeffrey G Reid; Jennifer Drummond; Kyle Chang; Yi Han; Lora R Lewis; Huyen Dinh; Christian J Buhay; Timothy Beck; Lee Timms; Michelle Sam; Kimberly Begley; Andrew Brown; Deepa Pai; Ami Panchal; Nicholas Buchner; Richard De Borja; Robert E Denroche; Christina K Yung; Stefano Serra; Nicole Onetto; Debabrata Mukhopadhyay; Ming-Sound Tsao; Patricia A Shaw; Gloria M Petersen; Steven Gallinger; Ralph H Hruban; Anirban Maitra; Christine A Iacobuzio-Donahue; Richard D Schulick; Christopher L Wolfgang; Richard A Morgan; Rita T Lawlor; Paola Capelli; Vincenzo Corbo; Maria Scardoni; Giampaolo Tortora; Margaret A Tempero; Karen M Mann; Nancy A Jenkins; Pedro A Perez-Mancera; David J Adams; David A Largaespada; Lodewyk F A Wessels; Alistair G Rust; Lincoln D Stein; David A Tuveson; Neal G Copeland; Elizabeth A Musgrove; Aldo Scarpa; James R Eshleman; Thomas J Hudson; Robert L Sutherland; David A Wheeler; John V Pearson; John D McPherson; Richard A Gibbs; Sean M Grimmond Journal: Nature Date: 2012-10-24 Impact factor: 49.962
Authors: Karen M Mann; Jerrold M Ward; Christopher Chin Kuan Yew; Anne Kovochich; David W Dawson; Michael A Black; Benjamin T Brett; Todd E Sheetz; Adam J Dupuy; David K Chang; Andrew V Biankin; Nicola Waddell; Karin S Kassahn; Sean M Grimmond; Alistair G Rust; David J Adams; Nancy A Jenkins; Neal G Copeland Journal: Proc Natl Acad Sci U S A Date: 2012-03-15 Impact factor: 11.205