Abstract
Abstract Pancreatic ductal Adenocarcinoma (PDAC) is a highly lethal solid tumor with 5-year survival rate of 5-8%. Extracellular vesicles like exosomes circulating in the blood are crucial mediators of intracellular communication, immunomodulation and tumor progression. The microRNAs being the major cargo of exosomes, are the primary carriers of intracellular information. The role of exosomal-miRNA (exoMIR’s) in regulating the pathogenesis of tumors is well-established in oncology but its potential is still unexplored. To the best of our knowledge no study has yet explored the contrasting exoMIR expression in cancer patients before and after their surgery. In this study, differential exoMIR’s profile of three pancreatic ductal adenocarcinoma patients at three stages: pre-surgery, post-surgery, and follow-up was established using small RNA sequencing on the Illumina platform. In blood samples taken before and after surgery total of 181, 201 and 201 microRNAs were dysregulated in circulating exosomes of three different patients viz. P_1, P_9 & P_11 (Patient identifiers) respectively. Out of the total dysregulated microRNAs in post-op samples 76 were upregulated and 105 downregulated in P_1, 95 upregulated and 106 downregulated in P_9 & 69 upregulated and 132 downregulated in P_11 as compared to their Pre surgery samples. Further, when exoMIR’s of post-op samples were compared to that of follow-up samples after 6 months of surgery their expression profile changed notably such that a total of 184, 157 & 190 microRNAs dysregulated in follow-up of P_1, P_9 and P_11 respectively. Out of the total dysregulated microRNAs in follow up samples 93 were upregulated and 91 downregulated in P_1, 69 upregulated and 88 downregulated in P_9 & 96 upregulated and 94 downregulated in P_11 as compared to their post-op samples. On Venn diagram analysis 27 microRNAs were found to be commonly dysregulated in all 3 patients before surgery and 22 common micro RNAs were again dysregulated even after 6 months of surgery. Bioinformatic analysis of these differentially expressed miRNAs and their respective protein targets revealed that their role in oncogenic molecular pathways is very prominent, thus highlighting their potential use in cancer therapeutics, diagnostics as well as prognosis. Citation Format: Rupinder Kaur, Sandeep Bhoriwal, Promod Kumar Gautam. Differential micro-RNA expression in circulating exosomes of pancreatic ductal adenocarcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2990.
Published Version
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