Abstract C047: UBE2C a poor prognostic biomarker in Black women with estrogen receptor positive (ER+) breast cancer in TCGA
Authors: Jones Veronica , Yuan Yate-Ching , Davis Melissa , Seewaldt Victoria , Kittles Rick 
Published: January 2023

Abstract
Introduction: The majority of estrogen receptor positive (ER+) breast cancer carry a good prognosis; however, there is a subset, luminal B breast cancer (LBC), that is highly aggressive. LBC is more common in Black/African American (BAA) women who have a four-times higher death rate from ER+ breast cancer compared to other races. There is evidence that LBC shares biologic similarities with triple negative breast cancer (TNBC); common differentially expressed genes have been identified in TNBC and LBC, particularly among BAA women. Specifically, ubiquitin-conjugating enzyme 2C (UBE2C) expression is elevated in both. UBE2C is a driver of the cell cycle and involved in Wnt/β-catenin signaling, epithelial to mesenchymal transition (EMT), invasion and metastasis. Here we interrogate the association of UBE2C mRNAseq expression with survival in BAA women with ER+ breast cancer in The Cancer Genome Atlas (TCGA). Methods: TCGA Breast (BRCA) cohorts were queried to investigate the differential UBE2C mRNA seq expression in normal vs tumor patient samples in the general breast cancer population and specifically in the ER+ patients. Expression was also compared across races (BAA vs. White). Kaplan-Meier (KM) curves were generated to determine overall survival by gene expression using median as threshold. Results: In TCGA, compared to normal (n=112), UBE2C mRNAseq expression was statistically significantly higher in tumor in all breast cancer patients (n=1092) as well as specifically in the ER+ cohort (n=805). UBE2C mRNAseq expression was higher in the ER- (n=237) compared to the ER+ breast cancer patients (n=805) (p=3.7e-45). Expression was also significantly higher in the progesterone receptor (PR) negative (n=342) compared to the PR positive patients (n=697) (p=1.89e-40). Higher UBE2C mRNAseq expression was associated with poorer disease-free survival in all breast cancer patients as well as specifically in the ER+ patients. When examining the BAA population compared to White, UBE2C mRNA seq expression was significantly higher among BAA (n=183) compared to White (n=753) patients (FC=1.9; p=6.02e-15). Genes involved in cell cycle pathways were significantly correlated with UBE2C mRNAseq expression among BAA ER+ patients (n=110) including CDCA5 (p=1.42e-26, r=0.81), CDK2 (p=1.13e-05, r=0.41), and CDK4 (p=4.67e-06, r=0.42). The proliferation gene MKI67 was also significantly correlated with UBE2C mRNA seq expression (p=6.24e-18, r=0.71). UBE2C mRNAseq high expression was significantly associated with poor progression-free survival for BAA patients with breast cancer (n=179, p= 0.0353). UBE2C mRNAseq high expression was positively associated with African ancestry and negatively associated with European ancestry. Conclusion: UBE2C is a poor prognostic marker in BAA women with ER+ breast cancer using the TCGA dataset. UBE2C plays an integral role in the cell cycle. Given the prevalence of resistance to cell cycle targets, such as CDK 4/6 inhibitors, UBE2C demonstrates a potential drug target to improve outcomes in LBC and mitigate disparities.
Citation Format: Veronica Jones, Yate-Ching Yuan, Melissa Davis, Victoria Seewaldt, Rick Kittles. UBE2C a poor prognostic biomarker in Black women with estrogen receptor positive (ER+) breast cancer in TCGA [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 C047.