Dataset Information

Downregulation of CYB5D2 is associated with breast cancer progression.

ABSTRACT: We report here that CYB5D2 is associated with tumor suppression function in breast cancer (BC). CYB5D2 expression was significantly reduced in tamoxifen resistant MCF7 cells and in MCF7 cell-derived xenografts treated with TAM. CYB5D2 overexpression induced apoptosis in MCF7 cells; CYB5D2 knockdown enhanced MCF7 cell proliferation. Using the TCGA and Curtis datasets within the Oncomine database, CYB5D2 mRNA expression was downregulated in primary BCs vs breast tissues and HER2-positive or triple negative BCs vs estrogen receptor (ER)-positive BCs. Using the TCGA and Metabric datasets (n?=?817 and n?=?2509) within cBioPortal, 660 and 4891 differentially expressed genes (DEGs) in relation to CYB5D2 were identified. These DEGs were enriched in pathways governing cell cycle progression, progesterone-derived oocyte maturation, oocyte-meiosis, estrogen-mediated S-phase entry, and DNA metabolism. CYB5D2 downregulation decreased overall survival (OS, p?=?0.0408). A CYB5D2-derived 21-gene signature was constructed and robustly correlated with OS shortening (p?=?5.72e-12), and independently predicted BC deaths (HR?=?1.28; 95% CI 1.08-1.52; p?=?0.004) once adjusting for known clinical factors. CYB5D2 reductions displayed relationship with mutations in PIK3CA, GATA3, MAP3K1, CDH1, TP53 and RB1. Impressively, 85% (560/659) of TP53 mutations occurred in the 21-gene signature-positive BC. Collectively, we provide the first evidence that CYB5D2 is a candidate tumor suppressor of BC.

SUBMITTER: Ojo D

PROVIDER: S-EPMC6488675 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Downregulation of CYB5D2 is associated with breast cancer progression.

Ojo Diane D Rodriguez David D Wei Fengxiang F Bane Anita A Tang Damu D

Scientific reports 20190429 1

We report here that CYB5D2 is associated with tumor suppression function in breast cancer (BC). CYB5D2 expression was significantly reduced in tamoxifen resistant MCF7 cells and in MCF7 cell-derived xenografts treated with TAM. CYB5D2 overexpression induced apoptosis in MCF7 cells; CYB5D2 knockdown enhanced MCF7 cell proliferation. Using the TCGA and Curtis datasets within the Oncomine database, CYB5D2 mRNA expression was downregulated in primary BCs vs breast tissues and HER2-positive or triple ...[more]

PMID: 31036830

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Dataset Information

Downregulation of CYB5D2 is associated with breast cancer progression.

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Downregulation of CYB5D2 is associated with breast cancer progression.

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