A predictive non-invasive SNP-based biomarker signature in resectable pancreatic cancer: protocol for a prospective validation study

• Published in: JMIR research protocols 2024-04
• Main Authors: Seeger, Nico, Gutknecht, Stefan, Zschokke, Irin, Fleischmann, Isabella, Roth, Nadja, Metzger, Jürg, Weber, Markus, Breitenstein, Stefan, Grochola, Lukasz Filip
• Format: Article
• Language: English
• ISSN: 1929-0748; 1929-0748

Single nucleotide polymorphisms (SNPs) are inherited genetic variants that can be easily determined in everyday clinical practice using a simple blood or even saliva test. They have the potential to serve as non-invasive biomarkers to predict cancer-specific patient outcomes after resection of pancreatic ductal adenocarcinoma (PDAC). Specifically, two recent analyses led to the identification and validation of three SNPs in the CD44 and CHI3L2 genes (SNPrs187115, SNPrs353630, SNPrs684559) that can be utilised as predictive biomarkers to help select patients who are likely to benefit from pancreatic resection. Those variants associate with an over 2-fold increased risk for tumour-related death in three independent PDAC study cohorts from Europe and U.S., including the publicly available Cancer Genome Atlas (TCGA) database (p-value up to 1x10-8). However, those analyses are limited by their retrospective study design with its inherent biases, such as selection and publication bias, which limits the utilization of these promising biomarkers in guiding PDAC therapy. In order to overcome the limitations of the previous, retrospectively-designed studies and translate the findings into clinical practice, we aim to utilise a cohort of PDAC patients who undergo pancreatic resection to prospectively validate the association of the identified SNPs with PDAC survival after resection in a controlled clinical setting. All patients with PDAC who undergo pancreatic resection at three participating hospitals in Switzerland 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. The follow-up data collection has started in August 2019 and the estimated end of data collection will be in May 2027. The study is still recruiting participants and 142 patients have been recruited as of November 2023. The DNA extraction and genotyping of the SNPs will be done after the inclusion of the last patient. Since no SNP genotypes have been determined, no data analysis has been performed yet. The results are expected to be published in 2027. This is the first prospective study of the CD44 and CH