Abstract C112: The carcinogenic role MCM10 in colorectal cancer progression and Hispanics' health disparities

Abstract Background: Hispanics represent over 17% of the U.S. population and face significant disparities in colorectal cancer (CRC) care, including delayed diagnosis, limited access to treatment, and poorer survival outcomes compared to non-Hispanic Whites (NHWs). Previous studies have identified MCM10 as a differentially expressed gene linked to poor outcomes in several cancers; however, its role in CRC remains poorly understood. This study investigated the role of MCM10 in CRC progression and its potential role in mediating ethnic disparities. Given that CRC is highly treatable when detected early, establishing MCM10 as a diagnostic biomarker and therapeutic target may improve early detection and treatment outcomes in underserved populations, thereby advancing equity in cancer care. Methods: MCM10 expression was assessed in CRC cell lines and tissue samples via qRT-PCR. The stage-specific expression patterns were analyzed using cDNA microarrays, while protein-level expression in tissues was examined through immunohistochemical analysis of tissue microarrays. The oncogenic role of MCM10 was further investigated through in vitro functional assays following gene knockdown. RNA sequencing (RS) and mass spectrometry (MS) were employed to elucidate the molecular pathways associated with MCM10 CRC carcinogenesis. To validate the translational relevance, these cellular findings were evaluated in a Hispanic CRC organoid model to identify an ethnicity-specific biomarker for this underserved population. Results: Our results demonstrated significant upregulation of MCM10 in CRC cell lines and tissues across both early and late stages compared to normal controls. Given the well-established Hispanic CRC health disparities in U.S., we assessed MCM10 as a potential ethnicity-specific biomarker. Notably, MCM10 expression was significantly upregulated in Hispanic patients compared to NHWs, including both early-onset and late-stage CRC. Functional assays revealed that MCM10 knockdown impaired CRC cell proliferation, invasion, and migration via cell cycle arrest and ROS-mediated apoptosis pathways. Integrated RS and MS identified PPFIA1 as a critical downstream effector of MCM10-driven oncogenic activity. To further validate these findings, we knocked out MCM10 in a Hispanic CRC organoid model, which led to a marked reduction in organoid size and viability via PPFIA1-mediated cell death. Conclusion: This study identifies MCM10 as a key oncogenic driver in CRC, highlighting its potential as a promising ethnicity-specific biomarker and therapeutic target for addressing CRC disparities in the Hispanic populations. Citation Format: Md Zahiru Islam Khan, Urbashi Basnet, Sourav Roy. The carcinogenic role MCM10 in colorectal cancer progression and Hispanics' health disparities [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C112.