Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Cancer Prev Res (Phila). 2013 Apr;6(4):321-30. doi: 10.1158/1940-6207.CAPR-12-0304. Epub 2013 Mar 19.
Risk biomarkers that are specific to estrogen receptor (ER) subtypes of breast cancer would aid the development and implementation of distinct prevention strategies. The contralateral unaffected breast of women with unilateral breast cancer (cases) is a good model for defining subtype-specific risk because women with ER-negative (ER-) index primaries are at high risk for subsequent ER-negative primary cancers. We conducted random fine needle aspiration of the unaffected breasts of cases. Samples from 30 subjects [15 ER-positive (ER+) and 15 ER- cases matched for age, race and menopausal status] were used for Illumina expression array analysis. Findings were confirmed using quantitative real-time PCR (qRT-PCR) in the same samples. A validation set consisting of 36 subjects (12 ER+, 12 ER- and 12 standard-risk healthy controls) was used to compare gene expression across groups. ER- case samples displayed significantly higher expression of 18 genes/transcripts, 8 of which were associated with lipid metabolism on gene ontology analysis (GO: 0006629). This pattern was confirmed by qRT-PCR in the same samples, and in the 24 cases of the validation set. When compared to the healthy controls in the validation set, significant overexpression of 4 genes (DHRS2, HMGCS2, HPGD and ACSL3) was observed in ER- cases, with significantly lower expression of UGT2B11 and APOD in ER+ cases, and decreased expression of UGT2B7 in both subtypes. These data suggest that differential expression of lipid metabolism genes may be involved in the risk for subtypes of breast cancer, and are potential biomarkers of ER-specific breast cancer risk.
针对乳腺癌雌激素受体 (ER) 亚型的风险生物标志物将有助于制定和实施不同的预防策略。患有单侧乳腺癌（病例）的女性的对侧未受影响的乳房是定义亚型特异性风险的良好模型，因为 ER 阴性（ER-）指数原发性乳腺癌的女性有很高的风险发生后续的 ER-原发性癌症。我们对病例的未受影响的乳房进行了随机细针抽吸。使用来自 30 名受试者（15 名 ER+和 15 名 ER-病例，按年龄、种族和绝经状态匹配）的样本进行 Illumina 表达谱分析。在相同样本中使用定量实时 PCR（qRT-PCR）验证发现。使用包含 36 名受试者（12 名 ER+、12 名 ER-和 12 名标准风险健康对照）的验证集来比较各组之间的基因表达。ER-病例样本显示 18 个基因/转录物的表达显著升高，其中 8 个基因在基因本体分析（GO：0006629）中与脂质代谢有关。这一模式在相同样本中的 qRT-PCR 中得到了证实，在验证集中的 24 例病例中也得到了证实。与验证集中的健康对照组相比，在 ER-病例中观察到 4 个基因（DHRS2、HMGCS2、HPGD 和 ACSL3）的显著过表达，而在 ER+病例中 UGT2B11 和 APOD 的表达显著降低，两种亚型的 UGT2B7 表达均降低。这些数据表明，脂质代谢基因的差异表达可能与乳腺癌亚型的风险有关，并且是 ER 特异性乳腺癌风险的潜在生物标志物。
