The VEGF-Hypoxia Signature Is Upregulated in Basal-like Breast Tumors from Women of African Ancestry and Associated with Poor Outcomes in Breast Cancer.

Autor:	Han YJ; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois., Liu S; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina., Hardeman A; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois., Rajagopal PS; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois., Mueller J; Department of Pathology, University of Chicago, Chicago, Illinois., Khramtsova G; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois., Sanni A; Department of Pathology and Forensic Medicine, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria., Ajani M; Department of Pathology, College of Medicine, University of Ibadan/University College Hospital, Ibadan, Oyo, Nigeria., Clayton W; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois., Hurley IW; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois., Yoshimatsu TF; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois., Zheng Y; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois., Parker J; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina., Perou CM; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina., Olopade OI; Center for Clinical Cancer Genetics and Global Health, Department of Medicine, University of Chicago, Chicago, Illinois.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Jun 03; Vol. 30 (11), pp. 2609-2618.
DOI:	10.1158/1078-0432.CCR-23-1526
Abstrakt:	Purpose: Black women experience the highest breast cancer mortality rate compared with women of other racial/ethnic groups. To gain a deeper understanding of breast cancer heterogeneity across diverse populations, we examined a VEGF-hypoxia gene expression signature in breast tumors from women of diverse ancestry. Experimental Design: We developed a NanoString nCounter gene expression panel and applied it to breast tumors from Nigeria (n = 182) and the University of Chicago (Chicago, IL; n = 161). We also analyzed RNA sequencing data from Nigeria (n = 84) and The Cancer Genome Atlas (TCGA) datasets (n = 863). Patient prognosis was analyzed using multiple datasets. Results: The VEGF-hypoxia signature was highest in the basal-like subtype compared with other subtypes, with greater expression in Black women compared with White women. In TCGA dataset, necrotic breast tumors had higher scores for the VEGF-hypoxia signature compared with non-necrosis tumors (P < 0.001), with the highest proportion in the basal-like subtype. Furthermore, necrotic breast tumors have higher scores for the proliferation signature, suggesting an interaction between the VEGF-hypoxia signature, proliferation, and necrosis. T-cell gene expression signatures also correlated with the VEGF-hypoxia signature when testing all tumors in TCGA dataset. Finally, we found a significant association of the VEGF-hypoxia profile with poor outcomes when using all patients in the METABRIC (P < 0.0001) and SCAN-B datasets (P = 0.002). Conclusions: These data provide further evidence for breast cancer heterogeneity across diverse populations and molecular subtypes. Interventions selectively targeting VEGF-hypoxia and the immune microenvironment have the potential to improve overall survival in aggressive breast cancers that disproportionately impact Black women in the African Diaspora. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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