Abstract 2071: Spatial tracking of the pre-metastatic niche in colorectal cancer

Abstract Lymph node metastatic positively correlates with poor prognosis of colorectal cancer. Thus, it is urgent to uncover the molecular mechanisms and develop better prediction criteria of the metastasis. Tumor budding refers to the presence of a cluster of tumor cells at the leading edge of tumor invasion and metastasis. This cluster is composed of either a single tumor cell or multiple tumor cells. Tumor budding is commonly observed in various types of cancer, including colorectal cancer (CRC), on histopathological slides. It is recognized as an independent predictive factor for lymph node metastasis and prognosis. In this study, the NanoString GeoMx equipment was applied to establish the expression profile of cancer transcriptomic atlas (CTA) in CRC specimens. According to the morphology of CRC tissues determined by markers including pancytokaretin, CD45, and alpha-smooth muscle actin, the regions of interest (ROIs) were categorized into four groups, including normal, deep tumor, superficial tumor, and budding-enriched area. With digital spatial analysis, we compared the CTA expression among the four groups of regions of interests (ROIs). We characterized a marker panel for tumor budding and poorly-differentiated clusters in CRC, which tracks the progression of CRC from normal part to tumor invasive front. Our data show that the tumor budding-enriched gene panel is primarily composed of genes regulating cytoskeleton, extracellular matrix (ECM), and some secreted factors. Furthermore, our data also indicate that a morphology-based gene panel better delineates the invasion progression. Those results allow us tracking the evolution of signaling transduction for metastasis from the primary tumor to tumor budding and subsequent distant metastasis, facilitating the development of targeted drugs aimed at preventing metastasis in colorectal cancer. Citation Format: Chun Hua Hung, Chung-Ta Lee, Yu-Min Yeh, Chun-Hui Lee, Wen-Tai Liu, Meng-Ru Shen, Peng-Chan Lin. Spatial tracking of the pre-metastatic niche in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2071.