Abstract
AbstractBackgroundA growing body of work suggests that inherited genetic variants can be utilized as non-invasive biomarkers to predict cancer-specific patient outcomes and guide therapy after resection of pancreatic ductal adenocarcinoma (PDAC). Specifically, two recent retrospective analyses led to the identification and retrospective validation of three single nucleotide polymorphisms (SNPs) in the CD44 and CHI3L2 genes (SNPrs187115, SNPrs353630, SNPrs684559) genes that can serve as predictive biomarkers to help select patients who are likely to benefit from pancreatic resection. Those SNPs have been shown to associate with an over 2-fold increased risk for tumour-related death in three independent PDAC study cohorts from Europe and the U.S (Hazard ratio (HR) up-to 0.38; p-value up-to 1x10−8).MethodsIn order to translate these retrospective findings into clinical practice, we aim to utilise a cohort of PDAC patients who undergo pancreatic resection in three hospitals in Switzerland to prospectively validate the association of the identified SNPs in the CD44 and CHI3L2 genes with PDAC survival after resection in a controlled clinical setting. All patients with a histopathological diagnosis of PDAC who undergo pancreatic resection and fulfil the inclusion criteria will be included consecutively. The SNP genotypes will be determined using standard genotyping techniques from patient blood samples. For each genotyped locus, log-rank and Cox multivariate regression tests will be performed, accounting for the relevant covariates AJCC-stage and resection-status. Clinical follow-up data will be collected for at least 3 years. Sample size calculation resulted in a number of 150 patients (80% power to detect allelic differences in survival; effect size>2.0 between genotypes; two-sided α-level of 0.05; drop-out rate of 10%; potential additional error margin of 10%).DiscussionThis is the first prospective study of the CD44 and CHI3L2 gene SNP-based biomarker signature in PDAC. A prospective validation of these biomarkers would enable its utilization as a non-invasive, predictive signature of survival after pancreatic resection that is readily available at the time of PDAC diagnosis. The results of this study may lead to improved patient outcomes in resectable PDAC.Trial registrationNot listed in a registry, because no results of a health care intervention are reported.
Publisher
Cold Spring Harbor Laboratory