Abstract 1933: Transcriptomic profiling of Hispanic colorectal cancer disparities
Authors: Nair Soumya , Kulkarni Aditi , Roy Sourav 
Published: April 2023

Colorectal cancer (CRC) was reported as the third most diagnosed cancer worldwide with approximately 1.93 million new cases reported in 2020. Within the U.S., the incidence and death rates differ by ethnicity. Among Hispanics, CRC accounted for 12% and 8% of all estimated new cases of cancer and 11% and 9% of all cancer deaths in men and women, respectively, in 2018. Though CRC is preventable, and the overall survival rate is approximately 90% when detected at early stages, only about 39% of CRC patients are diagnosed in the early stages, mostly because screening rates in the US are low, especially among Hispanics. Access to health care for Hispanics is limited when compared to non-Hispanic Whites (NHWs); as a result, they tend to present with later-stage CRC, which likely accounts for their inferior survival after CRC. Essential to improving treatment, prognosis, and detection strategies is the identification and validation of new ethnicity-specific transcriptomic profiles. Here, we have conducted RNA sequencing from Hispanic and NHW CRC (n=10 each) and normal adjacent tissues (NATs; n=3 each), to identify the differentially expressed genes (DEGs) in these two populations. The Illumina sequencing reads were mapped against the reference human genome, and the read counts were normalized using the median of ratios method using DESeq2 software. The transcriptomic analysis revealed that as compared to the respective NATs, 7222 and 7873 genes were observed to be differentially expressed in NHW and Hispanic CRC tissues. Among these, 213 and 363 genes were unique to the NHW and Hispanic CRC cohorts, respectively. Within the Hispanic cohort, gender-based analyses revealed that 504 and 266 genes were differentially expressed in the female and male donors (n=5 each), respectively, as compared to the NHW counterparts. Further, 271 and 475 genes were found to be differentially expressed in early (stage I/II; n=5) and late (stage III/IV; n=3) stages of Hispanic CRC tissues, respectively, as compared to the NHW counterparts. Pathway enrichment analysis of the unique DEGs from the Hispanic and NHW cohorts was conducted using Ingenuity Pathway Analysis software. The genes involved in cysteine biosynthesis, ferroptosis, and GABA receptor signaling pathways were seen to be enriched in the NHW cohort, whereas the genes involved in glucocorticoid receptor (GR) signaling, bile, and androgen biosynthesis pathways were enriched in the Hispanic cohort. Previous studies have implicated, GR signaling to promote tumor heterogeneity and invasion in CRC via CDK1, or bile acids to regulate numerous genes including p53, CDK1, cyclooxygenase 2, IL8, and various miRNAs leading to CRC metastasis. As each pathway likely regulates specific cellular behaviors, the DEGs identified from this study will constitute potential ethnicity-specific biomarkers or attractive targets for the development of novel therapeutic interventions.

Citation Format: Soumya Nair, Aditi Kulkarni, Sourav Roy. Transcriptomic profiling of 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 1933.