Christopher B Nahm1, John Turchini2, Nigel Jamieson3, Elizabeth Moon4, Loretta Sioson5, Malinda Itchins6, Jennifer Arena7, Emily Colvin8, Viive M Howell8, Nick Pavlakis9, Stephen Clarke9, Jaswinder S Samra10, Anthony J Gill11, Anubhav Mittal12. 1. The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, St. Leonards, NSW Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. 2. The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Cancer Diagnosis and Pathology, Kolling Institute, University of Sydney, Sydney, NSW, Australia. 3. Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. 4. Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. 5. Cancer Diagnosis and Pathology, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. 6. The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. 7. Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia. 8. The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia. 9. The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia. 10. The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, St. Leonards, NSW Australia; Sydney Vital, Kolling Institute, Sydney, NSW, Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia; Faculty of Medical and Health Sciences, Macquarie University, Sydney, NSW, Australia. 11. The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Cancer Diagnosis and Pathology, Kolling Institute, University of Sydney, Sydney, NSW, Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia; Faculty of Medical and Health Sciences, Macquarie University, Sydney, NSW, Australia. 12. The University of Sydney Northern Clinical School, Sydney, NSW, Australia; Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, St. Leonards, NSW Australia; Australian Pancreatic Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia; Faculty of Medical and Health Sciences, Macquarie University, Sydney, NSW, Australia. Electronic address: anubhav.mittal@sydney.edu.au.
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.
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.
Authors: Christopher B Nahm; John Turchini; Sumit Sahni; Elizabeth Moon; Malinda Itchins; Jennifer Arena; Angela Chou; Emily K Colvin; Viive M Howell; Nick Pavlakis; Stephen Clarke; Jaswinder S Samra; Anthony J Gill; Anubhav Mittal Journal: Cancers (Basel) Date: 2022-07-25 Impact factor: 6.575
Authors: Yongzhu Pu; Chun Wang; Sheng Zhao; Ran Xie; Lei Zhao; Kun Li; Conghui Yang; Rui Zhang; Yadong Tian; Lixian Tan; Jindan Li; Shujuan Li; Long Chen; Hua Sun Journal: Transl Cancer Res Date: 2021-07 Impact factor: 1.241