Abstract 2383: The stress survival gene CCNB1 drives colorectal cancer progression and represents a novel target to address ethnic disparities

Abstract Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the U.S., marked by significant racial and ethnic disparities in incidence, stage at diagnosis, and survival. While highly curable with early detection, Hispanics, who comprise over 17% of the U.S. population, face disproportionate barriers to timely diagnosis, leading to presentation with more advanced disease and poorer outcomes. This study investigates the functional role of the stress-survival pathway (SSP) gene, Cyclin B1 (CCNB1), as a potential early detection biomarker and therapeutic target to mitigate disparities between Hispanic and Non-Hispanic White (NHW) populations. Methods: Our investigation utilized a multi-platform approach, integrating computational and experimental cancer biology. Initial screening involved in-house in-silico RNA-sequencing, differential expression analysis of tumor and adjacent non-tumor CRC tissue samples, from Hispanic and NHW cohorts. CCNB1 was identified as one of the most differentially expressed gene among the two races. To validate this finding, we performed qRT-PCR in CRC cell lines and tissue samples. The stage-specific expression was further evaluated using cDNA microarray whereas protein-level expression was determined using immunohistochemical assay of tissue microarrays. The oncogenic role of CCNB1 was further evaluated in vitro using CRC cell lines, and highly translational patient derived organoid model after CCNB1 knockdown. The RNA sequencing and Mass spectrometry will subsequently be employed to identify underlying molecular mechanisms of CCNB1-mediated CRC progression. Results: Our results showed significant upregulation of CCNB1 in CRC cell lines and tissues at both transcript and protein levels. Notably, Hispanic CRC samples exhibited significantly higher expression of CCNB1 compared to NHWs, with marked upregulation of CCNB1 in early-onset and late-stage Hispanics. These results are in line with traditional delayed in diagnosis for Hispanic populations. The functional study demonstrated that CCNB1 knockdown in CRC cell lines significantly reduced proliferation, growth, invasion and migration of cells by inducing cell cycle arrest and apoptosis. In organoid model, the knockdown of CCNB1 reduced organoid growth by inducing apoptosis. In addition, multi-omics based molecular mechanisms associated with CCNB1-mediated cancer progression will be further evaluated using western blotting and qRT-PCR respectively. Conclusions: This study identifies CCNB1 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, Soumya Nair, Sourav Roy. The stress survival gene CCNB1 drives colorectal cancer progression and represents a novel target to address ethnic disparities abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2383.