Abstract C104: Unraveling the role of a stress-survival pathway gene MCM10 in Hispanic colorectal cancer disparities

Abstract Despite the advancement in screening and treatment strategies, colorectal cancer (CRC) remains the second leading cause of cancer-related mortality in the U.S., with significant disparities across racial/ethnic groups. Limited access to healthcare facilities and lower screening rates disproportionately affect Hispanics, leading to advanced-stage CRC diagnosis and subsequently lower overall survival rates. In a prior study using microarray and RNA-seq datasets from various databases, we identified 28 genes associated with stress-survival pathway (SSP) in CRC. The transcript-level expressions of these genes were analyzed in Hispanic (n=13) and NHW (n=19) tumors and corresponding non-tumor adjacent (NATs; Hispanic (n=5) and NHWs (n=6)) tissues by qRT-PCR. We observed that 14 SSP genes exhibited differential expression (BCL2L1, BCL2L12, CCNB1, CDK1, CSE1L, PDCD2L, ESPL1, GLA, GPX2, SLC7A11, TRIB3, NOXA, NQO1 and SH3GLB1) in CRC tissue samples from Hispanics compared to those from NHW individuals, suggesting their potential role in key cellular processes such as apoptosis regulation, cell cycle control, antioxidant defense, and cellular metabolism. BCL2L12, ESPL1, GPX1, NOXA, RRM2B, and SH3GLB1 were also differentially expressed in the Hispanic and NHW NATs; but their expression patterns differed in the respective tumor tissues suggesting their role in CRC development. With an increasing incidence of early-onset (individuals below 50 years) CRC cases, particularly known for its aggressive nature, and considering that Hispanics are the fastest-growing youngest ethnic group in the U.S., CRC disparities in Hispanics, is an extremely important problem to study. We further analyzed the expression patterns of SSP genes in early-onset (n=4) and late-stage (n=3) Hispanic CRC tissue samples compared to their respective NHW (early-onset (n=6); late-stage (n=11)) counterparts. Our study showed that eight genes (BCL2L12, CCNB1, CDC25, CDK1, GPX2, PRDX4, CSE1L, and NOXA) were differentially expressed in Hispanic CRC tissue from patients with an early-onset when compared to NHWs, suggesting their role cancer disparities especially related to early- onset of cancer among younger Hispanics individuals. Additionally, we observed the differential expression of three genes (MCM10, GPX2, and GLA) in late-stage Hispanic CRC tissues compared to NHWs indicating their potential role in the aggressiveness of late-stage CRC in the Hispanic population. Furthermore, we performed a functional analysis of the understudied gene MCM10 in CRC, which was differentially upregulated in Hispanic CRC tissues. Knockdown of MCM10 in two CRC cell lines (SW80 and Caco-2) revealed a significant decrease in various cellular processes including proliferation, invasion, migration, cell cycle, apoptosis, and ROS production. Our study suggests that certain SSP genes may have a role in Hispanic CRC disparities. Also, MCM10 plays a greater role in Hispanic CRC progression and has the potential to be used as an ethnicity-specific biomarker or therapeutic target for the Hispanic population. Citation Format: Sourav Roy, Urbashi Basnet, Md Zahirul Islam Khan. Unraveling the role of a stress-survival pathway gene MCM10 in Hispanic colorectal cancer disparities abstract. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C104.