1. Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma
- Author
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Jean-Baptiste Bachet, Jean Closset, J.-L. Van Laethem, Christophe Penna, Magali Svrcek, François Paye, Pieter Demetter, Philippe Rougier, Isabelle Salmon, Alain Sauvanet, Thierry André, C. Louvet, Jean-François Emile, F. Bonnetain, Raphaël Maréchal, Pascal Hammel, Armelle Bardier-Dupas, Jean-Christophe Vaillant, and Anne Couvelard
- Subjects
Adult ,Male ,Oncology ,Receptors, CXCR4 ,medicine.medical_specialty ,Kaplan-Meier Estimate ,Adenocarcinoma ,CXCR4 ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Aged ,Proportional Hazards Models ,Smad4 Protein ,Aged, 80 and over ,Tissue microarray ,Proportional hazards model ,business.industry ,Hazard ratio ,Hematology ,Middle Aged ,medicine.disease ,Pancreatic Neoplasms ,Treatment Outcome ,Chemotherapy, Adjuvant ,Lymphatic Metastasis ,Multivariate Analysis ,Cohort ,Disease Progression ,Biomarker (medicine) ,Female ,business - Abstract
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.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.High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR) = 1.74; P0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR = 2.19; P0.0001) 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).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.
- Published
- 2012
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