Gene Expression Profiling of Pancreatic Ductal Adenocarcinoma Arising From Intraductal Papillary Mucinous Neoplasms of the Pancreas

Abstract

ABSTRACT Introduction Intraductal papillary mucinous neoplasms (IPMNs) are diverse premalignant tumors of the pancreas. They progress stepwise from adenoma to carcinoma and offer an opportunity for intervention prior to malignant transformation into pancreatic ductal adenocarcinoma (PDAC). The current study aimed to identify differentially expressed genes (DEGs) in invasive PDAC‐associated IPMN vs. noninvasive IPMN to understand the potential molecular changes involved in malignant transformation of IPMN into PDAC. Materials and Methods Archived tissue and data from 12 patients with histologically proven invasive PDAC arising from IPMN specimens were assessed. Gene expression analysis was performed on RNA extracted from macro‐dissected tissue specimens using the NanoString nCounter PanCancer Progression assay. Statistical and pathway analysis was performed using SPSS v28 and Ingenuity Pathway Analysis, respectively. Results A total of 159 genes had significantly (p < 0.05, q < 0.05) different expression in PDAC arising from IPMN compared with that from IPMN alone (91 overexpressed and 68 underexpressed). Interestingly, 14 of top 10 over‐ and underexpressed genes were predicted to translate secretory proteins, with SignalP scores approaching 1. A number of differential canonical pathways (e.g., LXR/RXR activation pathway, glycolysis I gluconeogenesis I, and hepatic fibrosis) and potential upstream regulators (e.g., TGFB1, THBS2, etc.) were also identified. Conclusion A differential gene expression profile between PDAC arising from IPMN and IPMN alone was identified. Pathway analysis identified potential mechanisms involved in malignant transformation of IPMN to PDAC.

Keywords

• gene expression analysis
• intraductal pancreatic mucinous neoplasm (IPMN)
• molecular biomarkers
• pancreatic cysts
• pancreatic ductal adenocarcinoma
• pancreatic neoplasms