Abstract 6194: Evaluation of the differential expression profile of CXC-receptor-2 ligands for potential biomarker candidates in pancreatic ductal adenocarcinoma

Abstract

Abstract The major complexity of pancreatic cancer (PC) cases is late clinical presentation and metastasis at the time of detection. Achievement of significant clinical advancement in the treatment of PC disease needs extensive research efforts to discover early detection markers of this disease. In this study, we wanted to analyze the expression profile of different CXC-receptor 2 (CXCR2) ligands, well documented in the literature for their role in inflammation, in pancreatic ductal adenocarcinoma (PDAC) cases for the potential of biomarker candidates. With this perspective, we utilized different online portals to evaluate mRNA expression of different CXCR2 ligands CXCL1-3 and 5-8 in PDAC tumors in comparison with the normal pancreas. Analysis of GEO PDAC microarray dataset, GSE15471 containing 39 pancreatic tumors with corresponding matched normal samples, showed significantly higher expression of CXCL-3,5,6,8 in pancreatic tumors in comparison with their matched normal tissue. Similarly, analysis of next-generation sequenced transcriptomics data on MiPanda portal showed higher expression of CXCL-1,3,5,6,8 in pancreatic tumors of 417 PC patients in comparison with the normal pancreas. Interestingly, only CXCL5 ligand showed association with patient survival data based on the mRNA, miRNA, or lncRNA expression on Oncolnc-TCGA portal. PC patients with lower CXCL5 expression showed significantly higher survival in comparison with patients with higher CXCL5 expression. Next, we evaluated the expression pattern of CXCR2 ligands CXCL1, 3, and 8 in the human PC tissue specimens and using pancreatic tissues derived from disease progression mouse model of PDX-cre-LSL-KRASG12D. Immunohistochemical (IHC) analysis revealed positive staining for CXCL1, and 3 in both in the ducts and the stroma of the human PC tumors and normal pancreas specimens. However, in normal pancreas, the expression was localized only to the acinar cell compartment and pancreatic ducts were negative for expression. Overall the average composite score of CXCL3 IHC was higher in the PC tissue specimens versus the normal pancreas. Furthermore, we observed an increase in the expression of mCXCL1, 3, and 5 in the pre-cancerous lesions of tumors and metastasis derived from PDX-cre-LSL-KrasG12D. However, unlike the human tissues the normal murine pancreas was negative for the expression of mCXCL1 and 5. Lastly, mRNA expression analysis of nine different human PC cell lines showed higher CXCL2, 3, and 5 in cell lines derived from metastatic sites in comparison with cell lines derived from primary tumors. Our observations resonated with CXCL5 protein levels in these cell lines. In conclusion, our data suggest that among different CXCR2 ligands, CXCL5 shows the potential of being used as a biomarker in PC patients. Citation Format: Sugandha Saxena, Abhilasha Purohit, Evie Ehrhorn, Pranita Atri, Caitlin Molczyk, Michelle Varney, Rakesh K. Singh. Evaluation of the differential expression profile of CXC-receptor-2 ligands for potential biomarker candidates in pancreatic ductal 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 6194.