Abstract A075: Spatial genomic expression profiling reveals differential marker expression patterns in mucinous cystic carcinoma of the pancreas with ductal involvement

Abstract

Abstract Pancreatic cancer is a devastating disease with various subtypes, including the rare mucinous cystic carcinoma (MCC) of the pancreas. In this case report, we present a comprehensive spatial genomic expression analysis of MCC, focusing on the correlation between marker expression patterns and cystic versus ductal involvement. Using spatial genomics techniques, we assessed the expression of several markers in the cystic and ductal regions of MCC samples. Surprisingly, we found that the cystic region alone exhibited minimal expression of the MUC2 marker, while high expression of MUC2 was observed in the ductal region, irrespective of cystic involvement. Moreover, we identified a co-localization of high expression levels of REG4, FCGBP, TFF3, and S100A6 with MUC2 expression, suggesting a potential functional relationship in MCC pathogenesis. Notably, CLDN4 and SPINK4, markers previously associated with cystic carcinomas, exhibited predominant expression in the ductal region without cystic involvement. These findings suggest that MCC cases with ductal involvement may possess a more aggressive potential for developing into ductal adenocarcinoma. Interestingly, our analysis revealed that the expression of SPARC, a known tumor-related marker, did not show specific localization in either the ductal or cystic regions but exhibited coexpression with col1a1 and col1a2. This observation highlights potential interactions between SPARC and the extracellular matrix in MCC tumorigenesis. Contrary to previous studies focusing on cystic fluid aspirate, we did not observe significant genomic expression in the cystic fluid space. Additionally, we found that the expression of carcinoembryonic antigens CEACAM5/6, which are known serum markers for mucinous cystic neoplasm of the pancreas, were strongly expressed in the ductal region but not in the cystic regions. Surprisingly, we found that the expression levels of KRAS, a frequently mutated gene in pancreatic cancer, were insignificant in our MCC cases, suggesting alternative mechanisms driving tumorigenesis in this subtype. In conclusion, our findings indicate that mucinous cysts in MCC exhibit low mRNA expression levels, while the markers associated with cystic carcinoma demonstrate significant expression in the ductal region. These results suggest that MCC cases with ductal involvement may possess a greater potential for developing into the more aggressive ductal adenocarcinoma. Understanding the molecular characteristics of MCC can aid in identifying potential therapeutic targets and guiding personalized treatment strategies for this rare pancreatic cancer subtype. Citation Format: Arshia Ghodrati, Chirag S. Gopinath, Lusine Demirkhanyan, Manu Gnanamony, Joseph A. Norton, Sonia T. Orcutt, Christopher S. Gondi. Spatial genomic expression profiling reveals differential marker expression patterns in mucinous cystic carcinoma of the pancreas with ductal involvement [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A075.