CD 44 SNP rs 187115 : A novel biomarker signature that predicts survival in resectable pancreatic ductal adenocarcinoma

PURPOSE Although pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor, like other common cancers, it displays a wide range of biology. However, at present, there are no reliable tests to predict patients’ cancer-specific outcomes and guide personalized treatment decisions. In this study, we aim to identify such biomarkers in resectable PDAC by studying single nucleotide polymorphisms (SNPs) in the CD44 gene, which drives the progression of pancreatic cancer. EXPERIMENTAL DESIGN 348 PDAC patients from three independent cohorts (Switzerland, Germany, The Cancer Genome Atlas (TCGA)) who underwent pancreatic resection are included in the study. Information on the haplotype structure of the CD44 gene is obtained using 1000 Genomes Project data and the genotypes of the respective tagging SNPs are determined. Cox proportional hazards models are utilized to analyze the impact of SNP genotype on patients’ survival. RESULTS We identify a SNP in the CD44 gene (SNPrs187115) that independently associates with allelic differences in prognosis in all study cohorts. Specifically, in 121 Swiss patients, we observe an up-to 2.38-fold (p=0.020) difference in tumor-related death between the genotypes of SNPrs187115. We validate those results in both the German (hazard ratio (HR)=2.32, p=0.044, 101 patients) and the TCGA cohort (HR=2.36, p=0.044, 126 patients). CONCLUSIONS CD44 SNPrs187115 can serve as a novel biomarker readily available at the time of PDAC diagnosis that identifies patients at risk for faster tumor progression and guide personalized treatment decisions. It has the potential to significantly expand the pool of patients that would benefit from tumor resection. DOI: https://doi.org/10.1158/1078-0432.CCR-16-0058 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-125693 Accepted Version Originally published at: Stracquadanio, Giovanni; Vrugt, Bart; Flury, Renata; Schraml, Peter; Würl, Peter; Müller, Thomas H; Knippschild, Uwe; Henne-Bruns, Doris; Breitenstein, Stefan; Clavien, Pierre-Alain; Graf, Rolf; Bond, Gareth L; Grochola, Lukasz F (2016). CD44 SNP rs187115: A novel biomarker signature that predicts survival in resectable pancreatic ductal adenocarcinoma. Clinical Cancer Research:31. DOI: https://doi.org/10.1158/1078-0432.CCR-16-0058 1 CD44 SNP: A novel biomarker signature that predicts survival in resectable pancreatic ductal adenocarcinoma Giovanni Stracquadanio, Bart Vrugt, Renata Flury, Peter Schraml, Peter Würl, Thomas H. Müller, Uwe Knippschild, Doris Henne-Bruns, Stefan Breitenstein, PierreAlain Clavien, Rolf Graf, Gareth L. Bond, Lukasz F. Grochola Ludwig Institute for Cancer Research, University of Oxford, United Kingdom; Institute for Surgical Pathology, University Hospital of Zurich, Switzerland ; Institute for Pathology, Cantonal Hospital of Winterthur, Switzerland; Department of General and Visceral Surgery, Diakoniekrankenhaus Halle, Germany; German Red Cross Blood Transfusion Service NSTOB, Springe, Germany; Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany; Department of Visceraland Thoracic Surgery, Cantonal Hospital of Winterthur, Switzerland; Department of Visceral and Transplantation Surgery, University Hospital of Zurich, Switzerland. Running title: CD44 SNP predicts survival in PDAC