CD44 SNPrs187115: A Novel Biomarker Signature that Predicts Survival in Resectable Pancreatic Ductal Adenocarcinoma.
OBJECTIVE
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.


METHODS
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 SNPrs187115We 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 SNPrs187115can 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. Clin Cancer Res; 22(24); 6069-77. ©2016 AACR.
Ludwig Institute for Cancer Research, University of Oxford, Oxford, United Kingdom.
Giovanni
G
Stracquadanio
Institute for Surgical Pathology, University Hospital of Zurich, Zurich, Switzerland.
Bart
B
Vrugt
Institute for Pathology, Cantonal Hospital of Winterthur, Winterthur, Switzerland.
Renata
R
Flury
Institute for Surgical Pathology, University Hospital of Zurich, Zurich, Switzerland.
Peter
P
Schraml
Department of General and Visceral Surgery, Diakoniekrankenhaus Halle, Halle, Germany.
Peter
P
Würl
German Red Cross Blood Transfusion Service NSTOB, Springe, Germany.
Thomas H
TH
Müller
Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany.
Uwe
U
Knippschild
Department of General and Visceral Surgery, Ulm University Hospital, Ulm, Germany.
Doris
D
Henne-Bruns
Department of Visceral- and Thoracic Surgery, Cantonal Hospital of Winterthur, Winterthur, Switzerland.
Stefan
S
Breitenstein
Department of Visceral and Transplantation Surgery, University Hospital of Zurich, Zurich, Switzerland.
Pierre-Alain
PA
Clavien
Department of Visceral and Transplantation Surgery, University Hospital of Zurich, Zurich, Switzerland.
Rolf
R
Graf
Ludwig Institute for Cancer Research, University of Oxford, Oxford, United Kingdom.
Gareth L
GL
Bond
Department of Visceral and Transplantation Surgery, University Hospital of Zurich, Zurich, Switzerland. lukaszfilip.grochola@usz.ch.
Lukasz F
LF
Grochola
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D055815:Young Adult
D014408:Biomarkers, Tumor; C497483:CD44 protein, human; D018960:Hyaluronan Receptors