Mahauad-Fernandez Wadie D, Borcherding Nicholas C, Zhang Weizhou, Okeoma Chioma M
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America; Interdisciplinary Graduate program in Molecular and Cellular Biology (MCB), University of Iowa, Iowa City, Iowa, United States of America.
Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America; Medical Scientist Training Program, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America.
PLoS One. 2015 Apr 10;10(4):e0123931. doi: 10.1371/journal.pone.0123931. eCollection 2015.
Bone marrow stromal antigen 2 (BST-2) is a known anti-viral gene that has been recently identified to be overexpressed in many cancers, including breast cancer. BST-2 is critical for the invasiveness of breast cancer cells and the formation of metastasis in vivo. Although the regulation of BST-2 in immune cells is unraveling, it is unknown how BST-2 expression is regulated in breast cancer. We hypothesized that meta-analyses of BST-2 gene expression and BST-2 DNA methylation profiles would illuminate mechanisms regulating elevated BST-2 expression in breast tumor tissues and cells.
We performed comprehensive meta-analyses of BST-2 gene expression and BST-2 DNA methylation in The Cancer Genome Atlas (TCGA) and various Gene Expression Omnibus (GEO) datasets. BST-2 expression levels and BST-2 DNA methylation status at specific CpG sites on the BST-2 gene were compared for various breast tumor molecular subtypes and breast cancer cell lines.
We show that BST-2 gene expression is inversely associated with the methylation status at specific CpG sites in primary breast cancer specimens and breast cancer cell lines. BST-2 demethylation is significantly more prevalent in primary tumors and cancer cells than in normal breast tissues or normal mammary epithelial cells. Demethylation of the BST-2 gene significantly correlates with its mRNA expression. These studies provide the initial evidence that significant differences exist in BST-2 DNA methylation patterns between breast tumors and normal breast tissues, and that BST-2 expression patterns in tumors and cancer cells correlate with hypomethylated BST-2 DNA.
Our study suggests that the DNA methylation pattern and expression of BST-2 may play a role in disease pathogenesis and could serve as a biomarker for the diagnosis of breast cancer.
骨髓基质抗原2（BST-2）是一种已知的抗病毒基因，最近被发现它在包括乳腺癌在内的多种癌症中过表达。BST-2对于乳腺癌细胞的侵袭性以及体内转移灶的形成至关重要。尽管BST-2在免疫细胞中的调控机制正在逐步阐明，但尚不清楚其在乳腺癌中是如何被调控表达的。我们推测，对BST-2基因表达和BST-2 DNA甲基化谱进行荟萃分析，将有助于阐明乳腺肿瘤组织和细胞中BST-2表达升高的调控机制。
我们对癌症基因组图谱（TCGA）和多个基因表达综合数据库（GEO）中的BST-2基因表达和BST-2 DNA甲基化进行了全面的荟萃分析。比较了不同乳腺肿瘤分子亚型和乳腺癌细胞系中BST-2基因在特定CpG位点的表达水平和BST-2 DNA甲基化状态。
我们发现，原发性乳腺癌标本和乳腺癌细胞系中，BST-2基因表达与特定CpG位点的甲基化状态呈负相关。与正常乳腺组织或正常乳腺上皮细胞相比，BST-2去甲基化在原发性肿瘤和癌细胞中更为普遍。BST-2基因的去甲基化与其mRNA表达显著相关。这些研究提供了初步证据，表明乳腺肿瘤与正常乳腺组织之间的BST-2 DNA甲基化模式存在显著差异，并且肿瘤和癌细胞中的BST-2表达模式与BST-2 DNA低甲基化相关。
我们的研究表明，BST-2的DNA甲基化模式和表达可能在疾病发病机制中起作用，并可作为乳腺癌诊断的生物标志物。
