Abstract 3674: Differential expression of stress-survival pathway genes related to Hispanic colorectal cancer disparities

Abstract

Abstract Colorectal cancer (CRC) accounts for 12% and 8% of all estimated new cases of cancer and 11% and 9% of all cancer deaths in Hispanic men and women, respectively. Stress-survival pathways have been implicated in tumorigenesis of CRC and in providing resistance to chemotherapy-induced cell-death by suppressing reactive oxygen species (ROS), repairing DNA damage, and by regulating cell signaling pathways. However, studies related to the role of these pathways in CRC from the Hispanic health disparities perspective, are limited. Essential to improving treatment, prognosis, and detection strategies is the identification and validation of new ethnicity-specific transcriptomic markers within the stress-survival pathways as effective predictors of CRC. In this study, we have explored the role of stress-survival pathway genes in Hispanic and Non-Hispanic White (NHW) CRC tissues. We have used microarray and RNA-seq datasets obtained from the gene expression omnibus (GEO) and the cancer genome atlas (TCGA) to identify 28 genes associated with CRC. These genes were screened for transcript level expression in one normal colon and two CRC cell lines, and in cDNA arrays containing tumor (n=40) from different stages, and control (n=8) samples. The protein level expressions were evaluated by immunohistochemistry (IHC) in CRC tissue microarrays (TMAs) containing different stages of tumor (n = 108) and control (n = 12) tissues. All 28 genes were also analyzed for their transcript level expressions in Hispanic and NHW tissues. Genes related to apoptosis like FOXM1, CDK1, CDK4, Chek1, and MCM10 showed consistent upregulation in CRC cell lines, cDNA arrays and TMAs when compared to normal samples. We could also detect a correlation between the differential expression of these genes and the tumor stages. CDK4, Chek1, FOXM1, and CDC25, were observed to be downregulated in the Hispanic CRC tissues. On the other hand, oxidative stress markers were not seen to be differentially expressed in the two CRC cell lines when compared to the normal cell line. However, some of the known oxidative stress markers like PRDX4, GPX1, and SOD2 were found to be upregulated in Hispanics when compared to NHW tissues. Our results suggest that some of these stress-survival pathway genes could be explored as interesting candidates for ethnicity-specific CRC biomarkers and as novel therapeutic targets in the future. Citation Format: Aditi Kulkarni, Urbashi Basnet, Abhijeet R. Patil, Rebecca DeJesus, Sourav Roy. Differential expression of stress-survival pathway genes related to Hispanic colorectal cancer disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3674.