J B Bachet1, R Maréchal2, P Demetter3, F Bonnetain4, A Couvelard5, M Svrcek6, A Bardier-Dupas7, P Hammel8, A Sauvanet9, C Louvet10, F Paye11, P Rougier12, C Penna13, J C Vaillant14, T André15, J Closset16, I Salmon3, J F Emile17, J L Van Laethem2. 1. Medical University Pierre et Marie Curie, UFR Paris VI, Paris; EA4340 "Epidémiologie et oncogènes des tumeurs digestives", Versailles Saint-Quentin-en-Yvelines University, Versailles; Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, APHP, Paris, France; Department of Gastroenterology, Gastrointestinal cancer Unit, Erasme Hospital, Université Libre de Bruxelles, Brussels. Electronic address: jean-baptiste.bachet@psl.aphp.fr. 2. Department of Gastroenterology, Gastrointestinal cancer Unit, Erasme Hospital, Université Libre de Bruxelles, Brussels. 3. Department of Pathology, Erasme Hospital, Université Libre de Bruxelles, and DiaPath, Brussels, Belgium. 4. Department of Biostatistic and Epidemiology (EA 4184), Georges François Leclerc Center, Dijon. 5. Department of Pathology, Beaujon Hospital, APHP, Clichy. 6. Medical University Pierre et Marie Curie, UFR Paris VI, Paris; Department of Pathology, Saint Antoine Hospital, APHP, Paris. 7. Medical University Pierre et Marie Curie, UFR Paris VI, Paris; Department of Pathology, Pitié-Salpêtrière Hospital, APHP, Paris. 8. Department of Gastroenterology, Beaujon Hospital, APHP, Clichy. 9. Department of Surgery, Beaujon Hospital, APHP, Clichy. 10. Medical University Pierre et Marie Curie, UFR Paris VI, Paris; Department of Oncology, Saint Antoine Hospital, APHP, Paris; Department of Oncology, Institut Mutualiste Montsouris, Paris. 11. Medical University Pierre et Marie Curie, UFR Paris VI, Paris; Department of Surgery, Saint Antoine Hospital, APHP, Paris. 12. EA4340 "Epidémiologie et oncogènes des tumeurs digestives", Versailles Saint-Quentin-en-Yvelines University, Versailles; Department of Digestive Oncology, European Georges Pompidou Hospital, APHP, Paris. 13. EA4340 "Epidémiologie et oncogènes des tumeurs digestives", Versailles Saint-Quentin-en-Yvelines University, Versailles; Department of Surgery, Ambroise Paré Hospital, APHP, Boulogne-Billancourt. 14. Medical University Pierre et Marie Curie, UFR Paris VI, Paris; Department of Surgery, Pitié-Salpêtrière Hospital, APHP, Paris, France. 15. Medical University Pierre et Marie Curie, UFR Paris VI, Paris; Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, APHP, Paris, France. 16. Department of Surgery, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium. 17. EA4340 "Epidémiologie et oncogènes des tumeurs digestives", Versailles Saint-Quentin-en-Yvelines University, Versailles; Department of Pathology, Ambroise Paré Hospital, APHP, Boulogne-Billancourt, France.
Abstract
BACKGROUND: Prognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients. PATIENTS AND METHODS: A total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-β receptor, CXCR4, and LKB1. RESULTS: High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR) = 1.74; P < 0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR = 2.19; P < 0.0001) and was the strongest prognostic factor compared with clinicopathological factors. In patients who did not received adjuvant treatment, there was a trend toward decrease in the overall survival for negative Smad4 expression. Loss of Smad4 expression was not correlated with recurrence pattern but was shown to be predictive for adjuvant chemotherapy (CT) benefit (HR = 0.59; P = 0.002). CONCLUSIONS: CXCR4 is a strong independent prognostic biomarker associated with distant metastatic recurrence and appears as an attractive target to be evaluated in pancreatic adenocarcinoma. Negative SMAD4 expression should be considered as a potential predictor of adjuvant CT benefit.
BACKGROUND: Prognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients. PATIENTS AND METHODS: A total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-β receptor, CXCR4, and LKB1. RESULTS: High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR) = 1.74; P < 0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR = 2.19; P < 0.0001) and was the strongest prognostic factor compared with clinicopathological factors. In patients who did not received adjuvant treatment, there was a trend toward decrease in the overall survival for negative Smad4 expression. Loss of Smad4 expression was not correlated with recurrence pattern but was shown to be predictive for adjuvant chemotherapy (CT) benefit (HR = 0.59; P = 0.002). CONCLUSIONS:CXCR4 is a strong independent prognostic biomarker associated with distant metastatic recurrence and appears as an attractive target to be evaluated in pancreatic adenocarcinoma. Negative SMAD4 expression should be considered as a potential predictor of adjuvant CT benefit.
Authors: Stephan Kruger; Michael Haas; Steffen Ormanns; Sibylle Bächmann; Jens T Siveke; Thomas Kirchner; Volker Heinemann; Stefan Boeck Journal: World J Gastroenterol Date: 2014-08-21 Impact factor: 5.742
Authors: Ritu R Singh; Johanna Goldberg; Anna M Varghese; Kenneth H Yu; Wungki Park; Eileen M O'Reilly Journal: Cancer Treat Rev Date: 2019-03-22 Impact factor: 12.111