Abstract 5232: Differential expression of stress-survival pathway genes related to Hispanic colorectal cancer disparities

Abstract

Abstract Colorectal cancer (CRC) is one of the most life-threatening gastrointestinal cancers, with around 1.9 million new cases and 935,000 deaths in the year 2020 worldwide. It 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. Long-term cumulative exposure to environmental factors such as reactive oxygen species (ROS) has been implicated to cause molecular damage and DNA modifications that are critical for CRC pathogenesis through stress-survival pathway genes. However, limited number of studies related to the role of these pathways have not been conducted for the Hispanic population. The identification and validation of new ethnicity-specific transcriptomic markers within the stress-survival pathways is important for improving treatment, prognosis, and detection strategies. In this study, we have explored the role of stress-survival pathway genes in Hispanic and Non-Hispanic White (NHW) CRC tissues. In one of the previously published studies from our lab we used microarray and RNA-seq datasets obtained from the gene expression omnibus (GEO), the cancer genome atlas (TCGA), and the oncomine databases to identify 28 genes associated with CRC. These genes were screened for transcript level expressions in six CRC cell lines and a normal colon cell line, and in cDNA arrays containing the tumor (n=40) from different CRC stages, and control (n=8) samples by qRT-PCR. 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 (n=10) and NHW (n=10) tumors and corresponding non-tumor adjacent (NATs; n=3) tissues. The stress-survival pathway genes associated with cell cycle regulation such as CHEK1, MCM10, PDCD2L, CCNB1, CDK1 and CDK4, and an oxidative stress marker PRDX4 were upregulated at both transcript and protein levels when compared to its normal counterparts. Additionally, the genes CHEK1, MCM10, BCL2L1, CSE1L, ESPL1, GLA, GPX2, RRM2B, SH3GLB1, TNFRSF12A, TRAF5 and TRIB3 were observed to be upregulated whereas GPX1, NOXA, NQO1, SLC7A11, BCL2L12, CCNB1, CDK1, CDK4, FOXM1, PDCD2L and SOD2 were found to be downregulated in Hispanic tumor tissues when compared to NHWs. Only CDK1, CHEK1, FOXM1 and NQO1 were seen to be differentially expressed in the Hispanic and NHW NATs; however, their expression patterns were different from that observed in the respective tumor tissues. Overall, our current findings evaluate the expression of stress-survival pathway genes across different CRC cell lines, stages, and Hispanic and NHW tissues. The genes identified to be differentially expressed in Hispanic tissues may be used as potential biomarkers or as therapeutic targets specific to the Hispanic population in future. Citation Format: Urbashi Basnet, Aditi Kulkarni, Frances A. Rangel, Abhijeet R. Patil, 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 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5232.