Abstract LB472: Role of <i>PLCG2</i> in colorectal cancer development and progression

Abstract Colorectal cancer (CRC) has the fourth highest incident with the third highest mortality rate among all cancer types with global five-year survival rate of 65%. Although, due to advances in non-invasive imaging technologies, CRC can be detected at early stages, the number of incidents increase yearly. Therefore, uncovering new mechanism underlying CRC development and progression is crucial to provide improvement in making diagnostic and prognostic outcome assessment in the clinical field. For these reasons, we determined CRC tumor cell expression profiles in several publicly available scRNA-seq data sets. Interestingly, we found that although PLCG2 expression largely downregulated in most epithelial cells, some cells retained their expression. These PLCG2-High (PLCG2-H) cells found to be enriched in their proliferative and metastatic capabilities compared to PLCG2-Low (PLCG2-L) tumor epithelial cells. We tested our observations from scRNA-seq datasets in vitro by inducing suppression and over-expression of PLCG2 in human CRC cell lines. Our functional assays as well as RNA-seq analyses have shown that suppression of PLCG2 decreased migratory capacity of CRC cells, whereas over-expression of PLCG2 increased it. Finally, we try to verify our observations in ovo using chorioallantoic membrane (CAM) model. These findings suggest that retained PLCG2 levels could enable CRC cells to become more metastatic, and have the potential to be used as a biomarker to make improved prognostic outcome assessment for CRC patients. Citation Format: Onur Mert Batmaz, Xiaodong Wang, Patricia Raude, Vera Leidig, Dominik Saul, Robyn L. Kosinsky. Role of PLCG2 in colorectal cancer development and progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB472.