Abstract 1678: Establishment and characterization by expression microarrays of a patient-derived xenograft biobank for human pancreatic adenocarcinoma

Abstract

Abstract Pancreatic cancer survival rate is poor, with a 5-year survival rate of 7% in the Republic of Ireland. Over the last 40 years, pancreatic cancer is one of the only solid tumor types to have minimal improvement in patient outcome. In Ireland, pancreatic cancer surgical resection is limited to two hospitals: Cork University Hospital and St Vincent's University Hospital (SVUH) in Dublin. In collaboration with SVUH, we have established Ireland's only pancreatic cancer patient-derived xenograft (PDX) biobank program. Tumor material from candidate patients following surgical resection was cold transferred and implanted subcutaneously into CB17/Icr-Prkdcscid mice. At time of implant and continuation of generations, snap frozen material was collected. Using miRNA and mRNA microarray technology, matched adjacent normal tissue, original tumor material and first generation (F1) PDX tumor material was interrogated. Differential expression analysis was carried out on all samples with comparisons of normal, tumor and F1 generation. Across all comparisons there were approximately 4000 genes and miRNAs found to be differential expressed. In focusing on genes that were upregulated in tumor samples compared to normal and further upregulated in the PDX F1 samples compared to the tumor samples, we identified 88 genes of interest. Biological processes such as cell division, mitotic cell cycle processes and cell cycle processes characterized a significant number of these genes. Two of the key genes of interest in this analysis were TSPAN1 and TPX2. TSPAN1 was upregulated 9.5-fold in tumor-normal comparison and upregulated a further 2.3-fold in the PDX F1 compared to the patient tumor. TPX2 was upregulated 4.4-fold in the tumor-normal comparison and a further 3.9-fold increase in the PDX tumor compared to patient tumor. TSPAN1 has previously been shown to increase the metastatic and invasive potential of pancreatic ductal adenocarcinoma cell lines. TPX2, a microtubule-associated protein, has been shown to reduce tumor growth in vivo when silenced. The pancreatic PDX biobank represents a versatile, expandable patient cohort for preclinical investigation. Analysis of gene expression profiles of normal vs tumor and tumor Vs PDX showed genes with associated tumor proliferation and aggressiveness. Citation Format: Sandra Roche, Fiona O'Neill, Niall Swan, Ninfa L. Straubinger, Neil T. Conlon, Jean Murphy, Kevin Conlon, Ray McDermott, Justine Meiller, Justin Geoghegan, Michael Moriarty, Robert M. Straubinger, Martin Clynes. Establishment and characterization by expression microarrays of a patient-derived xenograft biobank for human pancreatic adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1678.