Abstract C105: Novel cancer-specific hypoxia signature predicts poor prognosis and highlights racial disparities in breast cancer

Abstract Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. TNBC displays exceptional transcriptional heterogeneity, both between patients and intratumorally, and disproportionately affects underserved women. Hypoxia, a state of low oxygen levels, is often present in the solid tumor microenvironment. In TNBC, hypoxia is a key driver of aggressiveness and therapeutic resistance. Past bulk RNA sequencing (RNAseq) studies in cancer research have lacked spatial resolution, failing to uncover precise transcriptional differences within tumor regions. This spatial limitation has been especially problematic for studying transcriptional heterogeneity of the cellular hypoxia response within tumors. By integrating single-cell RNA sequencing and spatial transcriptomic analyses in a TNBC xenograft tumor model, our research has uncovered a novel hypoxia gene signature, specific to cancer cells. Elevated expression of this hypoxia signature predicts poorer prognosis in breast cancer patients, especially within TNBC patients and those of African ancestry. This suggests that hypoxia may play a role in the racial disparities observed in TNBC prognosis, potentially informing treatment strategies. This workflow introduces a novel framework for translating general spatial transcriptomics data into clinically relevant and accurate gene signatures. Citation Format: Kent Schechter, Long C. Nguyen, Geetha P. Yerradoddi, Rania Bassiouni, John D. Carpten, Marsha R. Rosner. Novel cancer-specific hypoxia signature predicts poor prognosis and highlights racial disparities in breast cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C105.