CD44 SNPrs187115: a novel biomarker signature that predicts survival in resectable pancreatic ductal adenocarcinoma

Research output: Contribution to journalArticlepeer-review

Authors

  • Giovanni Stracquadanio
  • Bart Vrugt
  • Renata Flury
  • Peter Schraml
  • Peter Würl
  • Thomas H Müller
  • Uwe Knippschild
  • Doris Henne-Bruns
  • Stefan Breitenstein
  • Pierre-Alain Clavien
  • Rolf Graf
  • Lukasz F Grochola

Colleges, School and Institutes

External organisations

  • University of Oxford
  • University Hospital Zürich
  • Institute for Pathology, Cantonal Hospital of Winterthur, Winterthur, Switzerland.
  • Department of General and Visceral Surgery, Diakoniekrankenhaus Halle, Halle, Germany.
  • German Red Cross Blood Transfusion Service NSTOB, Springe, Germany.
  • Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany.
  • Department of Visceral- and Thoracic Surgery, Cantonal Hospital of Winterthur, Winterthur, Switzerland.

Abstract

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 SNPs in the CD44 gene, which drives the progression of pancreatic cancer.

Experimental Design: A total of 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 an 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 (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. 

Bibliographic note

©2016 American Association for Cancer Research.

Details

Original languageEnglish
Pages (from-to)6069-6077
Number of pages9
JournalClinical Cancer Research
Volume22
Issue number24
Early online date9 Jun 2016
Publication statusPublished - Dec 2016

Keywords

  • Adenocarcinoma/genetics, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor/genetics, Carcinoma, Pancreatic Ductal/genetics, Cohort Studies, Disease Progression, Female, Gene Expression Regulation, Neoplastic/genetics, Humans, Hyaluronan Receptors/genetics, Male, Middle Aged, Pancreatic Neoplasms/genetics, Polymorphism, Single Nucleotide/genetics, Prognosis, Proportional Hazards Models, Young Adult