Abstract 1137: Spatial expression profile of mucinous cystic neoplasm indicates a divergent malignant marker patterns in ductal and stromal regions
Authors: Arshia Ghodrati, Chirag S. Gopinath, Amin Parvizi, Manu Gnanamony, Lusine Demirkhanyan, Christopher S. Gondi
Journal: Cancer Research (2024)

Abstract Mucinous cystic pancreatic neoplasms (MCPN), initially characterized as benign, present a unique challenge, with the five-year survival rate dropping from 100% to 57% if malignancy occurs. In this study, we using spatial genomic expression analysis of MCPN, and focus on the correlations between marker expression patterns in stroma and ductal region. Tissues obtained from surgical samples of a 69-year-old patient with a pancreatic head cystic mass and a history of pancreatitis (staged as T3N1Mx) were embedded in paraffin. These tissues were then sectioned, collected onto subbed slides, and subjected to probe hybridization, ligation, and extraction onto Visum slides following the manufacturer's instructions (10X Genomics). Genomic expression was extracted using established protocols, processed through SpaceRanger, and further visualized in Loupe Browser (10X Genomics). A comparison was conducted between the ductal and stromal regions, both with and without cystic involvement. Our study reveals a significant 5.1 log2 fold increase in MUC5AC expression in the ductal region, regardless of cystic involvement, suggesting implications for apoptosis regression and cadherin-dependent cell adhesion in MCPN progression. Further analysis indicates a significantly higher expression of TMSB4X exclusively in the ductal region, extending into the surrounding stroma, potentially stimulating MCPN progression by fostering pro-inflammatory cytokine environments. The novel marker IGKC, indicating favorable prognosis and PDAC treatment efficacy, shows high expression in the stroma (1.8 log2 fold higher). However, around the duct with cystic involvement, its expression is notably reduced (-1.7 log2 fold lower), suggesting pathways that may contribute to MCPN's progression towards a more invasive PDAC phenotype. Additionally, our study reveals a 1.9 log2 fold elevated expression of FN1, a biomarker associated with poor outcomes in PDAC patients, in the stroma around the cyst, hinting at a possible pathogenic role of FN1 in cell adhesion, migration, and progression of MCPN to PDAC. Co-expression of FN1 with COMP and TIMP3 within MCPN suggests a concerted effort in the microenvironment, influencing tissue development, maintenance, and extracellular matrix remodeling. Co-localization of FN1 with COMP and TIMP3, particularly within degenerating acinar cells, hints at a potential mechanism in the intricate progression of MCPN to PDAC. These findings contribute to a deeper understanding of the molecular landscape of MCPN, offering potential avenues for targeted interventions to thwart its progression to PDAC, guiding novel diagnostic and therapeutic strategies for pancreatic neoplasms. Further expression data will be presented. Citation Format: Arshia Ghodrati, Chirag S. Gopinath, Amin Parvizi, Manu Gnanamony, Lusine Demirkhanyan, Christopher S. Gondi. Spatial expression profile of mucinous cystic neoplasm indicates a divergent malignant marker patterns in ductal and stromal regions [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 1137.