Molecular Diagnostics Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
PLoS One. 2010 Feb 9;5(2):e9122. doi: 10.1371/journal.pone.0009122.
This study was initiated to identify biomarkers with potential value for the early detection of poor-outcome breast cancer. Two sets of well-characterized tissues were utilized: one from breast cancer patients with favorable vs. poor outcome and the other from healthy women undergoing reduction mammaplasty. Over 46 differentially expressed genes were identified from a large list of potential targets by a) mining publicly available expression data (identifying 134 genes for quantitative PCR) and b) utilizing a commercial PCR array. Three genes show elevated expression in cancers with poor outcome and low expression in all other tissues, warranting further investigation as potential blood markers for early detection of cancers with poor outcome. Twelve genes showed lower expression in cancers with poor outcome than in cancers with favorable outcome but no differential expression between aggressive cancers and most healthy controls. These genes are more likely to be useful as prognostic tissue markers than as serum markers for early detection of aggressive disease. As a secondary finding was that, when histologically normal breast tissue was removed from a distant site in a breast with cancer, 7 of 38 specimens displayed a cancer-like expression profile, while the remaining 31 were genetically similar to the reduction mammaplasty control group. This finding suggests that some regions of ipsilateral histologically 'normal' breast tissue are predisposed to becoming malignant and that normal-appearing tissue with malignant signature might warrant treatment to prevent new primary tumors.
本研究旨在鉴定具有潜在价值的生物标志物，用于早期发现预后不良的乳腺癌。我们使用了两组特征明确的组织：一组来自预后不良和预后良好的乳腺癌患者，另一组来自接受乳房缩小术的健康女性。通过 a) 挖掘公开可用的表达数据（鉴定出用于定量 PCR 的 134 个基因）和 b) 利用商业 PCR 阵列，从大量潜在靶标中确定了超过 46 个差异表达基因。有三个基因在预后不良的癌症中表达升高，而在所有其他组织中表达降低，这三个基因作为早期发现预后不良癌症的潜在血液标志物，值得进一步研究。有 12 个基因在预后不良的癌症中的表达低于预后良好的癌症，但在侵袭性癌症和大多数健康对照之间没有差异表达。这些基因作为预后组织标志物比作为早期检测侵袭性疾病的血清标志物更有用。此外，我们还发现，当从患有癌症的乳房的远处部位切除组织学正常的乳腺组织时，38 个标本中有 7 个显示出类似癌症的表达谱，而其余 31 个标本与乳房缩小术对照组在基因上相似。这一发现表明，同侧组织学“正常”乳腺组织的某些区域易发生恶性转化，并且具有恶性特征的外观正常组织可能需要治疗以预防新的原发性肿瘤。
