Abstract 4957: Oncogenic role of stress survival gene MCM10 in colorectal cancer progression and Hispanics health disparities

Abstract Background: Colorectal cancer (CRC) remains the second leading cause of cancer mortality in the U.S., with significant racial and ethnic disparities. This study investigates the role of a stress-survival pathway (SSP) gene MCM10 in CRC, particularly focusing on disparities between Hispanics and Non-Hispanic Whites (NHWs) in late-stage carcinogenesis. Despite comprising over 17% of the U.S. population, Hispanics face significant healthcare inequities, particularly in cancer diagnosis, leading to delayed CRC detection and reduced survival rates. Since CRC is highly treatable when identified early, addressing these disparities is therefore very crucial. Establishing MCM10 as a diagnostic biomarker and therapeutic target could significantly improve CRC management and outcomes in underserved populations. Methods: Our in-silico analysis previously identified MCM10 as a differentially expressed SSP gene associated with CRC progression. To validate this finding, we analyzed MCM10 expression in CRC cell lines and tissue samples using qRT-PCR. The stage-specific expression patterns were further assessed through cDNA microarray analysis, while protein-level expression was confirmed via immunohistochemical assay of tissue microarrays. Functional studies were conducted in vitro after MCM10 knockdown to investigate the role of MCM10 in critical cancer-related processes such as proliferation, invasion, and survival. RNA sequencing and mass spectrometry were subsequently employed to identify the molecular mechanisms underlying MCM10-driven CRC progression. Results: Our results showed significant upregulation of MCM10 in CRC cell lines and tissues at both transcript and protein levels. Notably, Hispanic CRC samples exhibited differential expression of MCM10 compared to NHWs, with marked upregulation of MCM10 in late-stage Hispanics. These results are in line with their traditional late-stage diagnosis. The functional study demonstrated that MCM10 knockdown in CRC cell lines significantly reduced proliferation, growth, invasion and migration of cells by inducing cell cycle arrest, apoptosis and reactive oxygen species pathways. In addition, our integrative RNA-sequencing and proteomics study reported two novel genes from zinc finger family along with 17 additional proteins which could be associated with MCM10 mediated carcinogenesis. Conclusion: This study identifies MCM10 as a key oncogenic driver in CRC, highlighting its potential as a diagnostic biomarker and therapeutic target to enhance disease management and reduce ethnic disparities in outcomes among Hispanics and NHWs. Citation Format: Md Zahirul Islam Khan, Urbashi Basnet, Sourav Roy. Oncogenic role of stress survival gene MCM10 in colorectal cancer progression and Hispanics health disparities [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 4957.