Abstract IA027: Role of stress-survival pathways and transcriptomic alterations in progression of colorectal cancer: A Hispanic health disparities perspective

Abstract

Abstract Essential to improving treatment, prognosis, and detection strategies are the identification and validation of new ethnicity-specific genomic profiles in cellular stress and survival pathways as effective predictors of colorectal cancer (CRC). These pathways are increasingly implicated in tumorigenesis of CRC and in providing resistance to chemotherapy-induced cell death. In this study, we have explored the role of these pathways in the biological significance of the expression of stress-survival pathway-associated genes in CRC progression and their role in promoting tumor aggressiveness from the Hispanic health disparities perspective. Transcript expression of oxidative stress and apoptosis-associated gene was evaluated in CRC gene microarray and RNAseq datasets to obtain 28 target genes. These genes were screened for transcript-level expression in six CRC cell lines and cDNA arrays containing the tumor (n=40) from different stages, and control (n=8) samples. The protein expression was evaluated by immunohistochemistry (IHC) in CRC microarrays (TMAs) containing different stages of tumor (n = 108) and control (n = 12) tissues. Target genes were also analyzed in Hispanic and Non-Hispanic White (NHWs) tissues at the transcript level. The analysis of target genes FOXM1, CDK1, CDK4, Chek1, and MCM10 showed consistent upregulation in CRC cell lines, cDNA arrays, and TMAs. The differential expression was also associated with the tumor stages. Among the target genes, Chek1, MCM10, and FOXM1 were found to be differentially expressed in Hispanic tissues when compared to the NHW samples. No significant difference was observed in the expression levels of CDK1 and CDK4 between the Hispanic and NHW tissues. Eight genes that did not show differential expression in CRC cell lines, were also seen to be upregulated in the Hispanic tissues, suggesting the influence of ethnicity-specific genetic makeup on the expression of these genes. The genes identified to be upregulated in Hispanic tissues may be used as potential biomarkers or as therapeutic targets in the Hispanic population. Citation Format: Aditi Kulkarni, Urbashi Basnet, Frances Rangel, Sourav Roy. Role of stress-survival pathways and transcriptomic alterations in progression of colorectal cancer: A Hispanic health disparities perspective [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA027.