Nahm, C. B. et al. (2019) Biomarker panel predicts survival after resection in pancreatic ductal adenocarcinoma: a multi-institutional cohort study. European Journal of Surgical Oncology, 45(2), pp. 218-224. (doi: 10.1016/j.ejso.2018.10.050) (PMID:30348604)
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Abstract
Background: Up to 60% of patients who undergo curative-intent pancreatic ductal adenocarcinoma (PDAC) resection experience disease recurrence within six months. We recently published a systematic review of prognostic immunohistochemical biomarkers in PDAC and shortlisted a panel of those reported with the highest level of evidence, including p53, p16, Ca-125, S100A4, FOXC1, EGFR, mesothelin, CD24 and UPAR. This study aims to discover and validate the prognostic significance of a combinatorial panel of tumor biomarkers in patients with resected PDAC. Methods: Patients who underwent PDAC resection were included from a single institution discovery cohort and a multi-institutional validation cohort. Tumors in the discovery cohort were stained immunohistochemically for all nine shortlisted biomarkers. Biomarkers significantly associated with overall survival (OS) were reevaluated as a combinatorial panel in both discovery and validation cohorts for its prognostic significance. Results: 224 and 191 patients were included in the discovery and validation cohorts, respectively. In both cohorts, S100A4, Ca-125 and mesothelin expression were associated with shorter OS. In both cohorts, the number of these biomarkers expressed was significantly associated with OS (discovery cohort 36.8 vs. 26.4 vs 16.3 vs 12.8 months, P < 0.001; validation cohort 25.2 vs 18.3 vs 13.6 vs 11.9 months, P = 0.008 for expression of zero, one, two and three biomarkers, respectively). On multivariable analysis, expression of at least one of three biomarkers was independently associated with shorter OS. Conclusion: Combinations of S100A4, Ca-125 and mesothelin expression stratify survival after resection of localized PDAC. Co-expression of all three biomarkers is associated with the poorest prognostic outcome.
| Item Type: | Articles |
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| Additional Information: | Christopher B Nahm is a recipient of the following scholarships: 2018 Australian Pancreatic Centre Harris Van Beek Scholarship, 2018 Sydney Vital Scholar Award, 2018 Australia New Zealand Hepatic Pancreatic and Biliary Association Research Scholarship, and 2018 Sydney Upper Gastrointestinal Surgical Society Travel Grant. The Australian Pancreatic Genome Initiative (APGI) provided tissue microarrays for the validation cohort. The APGI BioResource is supported by the Avner Pancreatic Cancer Foundation. |
| Keywords: | Biomarker, pancreatectomy, pancreatic cancer, survival. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Jamieson, Professor Nigel |
| Authors: | Nahm, C. B., Turchini, J., Jamieson, N., Moon, E., Sioson, L., Itchins, M., Arena, J., Colvin, E., Howell, V. M., Pavlakis, N., Clarke, S., Samra, J. S., Gill, A. J., and Mittal, A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | European Journal of Surgical Oncology |
| Publisher: | Elsevier |
| ISSN: | 0748-7983 |
| ISSN (Online): | 1532-2157 |
| Published Online: | 11 October 2018 |
| Copyright Holders: | Copyright © 2018 Elsevier Ltd. |
| First Published: | First published in European Journal of Surgical Oncology 45(2): 218-224 |
| Publisher Policy: | Reproduced in accordance with the publisher copyright policy |
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