Vallega Karin A, Liu NingNing, Myers Jennifer S, Yu Kaixian, Sang Qing-Xiang Amy
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida, United States of America.
Department of Statistics, Florida State University, Tallahassee, Florida, United States of America.
PLoS One. 2016 Jun 17;11(6):e0157741. doi: 10.1371/journal.pone.0157741. eCollection 2016.
African American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels have not been compared between AA and CA patients in a stage- and subtype-specific context. Breast cancer prognosis and treatments vary by subtype. This work investigates differential resistin gene expression in human breast cancer tissues of specific stages, receptor subtypes, and menopause statuses in AA and CA women.
Differential gene expression analysis was performed using human breast cancer gene expression data from The Cancer Genome Atlas. We performed inter-race resistin gene expression level comparisons looking at receptor status and stage-specific data between AA and CA samples. DESeq was run to test for differentially expressed resistin values.
Resistin RNA was higher in AA women overall, with highest values in receptor negative subtypes. Estrogen-, progesterone-, and human epidermal growth factor receptor 2- negative groups showed statistically significant elevated resistin levels in Stage I and II AA women compared to CA women. In inter-racial comparisons, AA women had significantly higher levels of resistin regardless of menopause status. In whole population comparisons, resistin expression was higher among Stage I and III estrogen receptor negative cases. In comparisons of molecular subtypes, resistin levels were significant higher in triple negative than in luminal A breast cancer.
Resistin gene expression levels were significantly higher in receptor negative subtypes, especially estrogen receptor negative cases in AA women. Resistin may serve as an early breast cancer biomarker and possible therapeutic target for AA breast cancer.
被诊断患有乳腺癌的非裔美国(AA)女性更有可能患侵袭性亚型。研究不同患者群体之间的差异表达基因可能有助于解释种族健康差异。抵抗素就是这样一种基因,它与炎症、肥胖和乳腺癌风险有关。先前的研究表明,与美国白人(CA)患者相比,AA乳腺癌患者血清和组织中的抵抗素表达更高。然而,尚未在特定阶段和亚型的背景下比较AA和CA患者之间的抵抗素表达水平。乳腺癌的预后和治疗因亚型而异。这项工作研究了AA和CA女性特定阶段、受体亚型和绝经状态的人乳腺癌组织中抵抗素基因的差异表达。
使用来自癌症基因组图谱的人类乳腺癌基因表达数据进行差异基因表达分析。我们进行了种族间抵抗素基因表达水平比较,观察AA和CA样本之间的受体状态和阶段特异性数据。运行DESeq以测试差异表达的抵抗素值。
总体而言,AA女性的抵抗素RNA更高,在受体阴性亚型中值最高。与CA女性相比,雌激素、孕激素和人表皮生长因子受体2阴性组在I期和II期AA女性中显示出抵抗素水平有统计学意义的升高。在种族间比较中,无论绝经状态如何,AA女性的抵抗素水平都显著更高。在全人群比较中,I期和III期雌激素受体阴性病例中抵抗素表达更高。在分子亚型比较中,三阴性乳腺癌中的抵抗素水平显著高于管腔A型乳腺癌。
受体阴性亚型中抵抗素基因表达水平显著更高,尤其是AA女性中的雌激素受体阴性病例。抵抗素可能作为AA乳腺癌的早期生物标志物和可能的治疗靶点。