Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue.
Proliferative genes dominate malignancy-risk gene signature in histologically-normal breast tissue.
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DOI：
10.1007/s10549-009-0344-y
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发表时间：
2010-01
影响因子：
3.8
通讯作者：
Yeatman, Timothy
中科院分区：
文献类型：
--
作者：
Chen, Dung-Tsa;Nasir, Aejaz;Culhane, Aedin;Venkataramu, Chinnambally;Fulp, William;Rubio, Renee;Wang, Tao;Agrawal, Deepak;McCarthy, Susan M.;Gruidl, Mike;Bloom, Gregory;Anderson, Tove;White, Joe;Quackenbush, John;Yeatman, Timothy
历史数据表明，组织学正常的乳腺在分子水平可能存在癌前病变。我们推测，具有“肿瘤样”基因表达模式的组织学正常组织可能对未来癌症的发生具有重大风险。与这些高风险组织相关的基因被视为“恶性风险基因”。
我们从总共90名乳腺癌患者中收集了一组143个来自接受根治性乳房切除术的乳腺癌患者的组织学正常的乳腺组织，以及一组42个不同组织学分级的浸润性导管癌（IDC）。使用微阵列分析评估所有样本的全基因表达差异。在本研究中，我们将正常乳腺组织定义为包括组织学正常和良性病变。
在此我们报告了一种“恶性风险”基因特征的发现，它可能预示着良性但分子异常的乳腺组织中乳腺癌发生的风险。通路分析表明，恶性风险特征中具有增殖功能的基因显著富集，但似乎与雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体2（HER2）状态无关。该特征通过逆转录聚合酶链反应（RT - PCR）得到验证，与微阵列数据具有高度相关性（皮尔逊相关系数 = 0.95，p < 0.0001）。
这些结果表明恶性风险特征在正常乳腺组织中具有预测作用。增殖生物学在肿瘤发展的早期阶段起主导作用。
Historical data have indicated the potential for the histologically-normal breast to harbor pre-malignant changes at the molecular level. We postulated that a histologically-normal tissue with “tumor-like” gene expression pattern might harbor substantial risk for future cancer development. Genes associated with these high-risk tissues were considered to be “malignancy-risk genes”. From a total of 90 breast cancer patients, we collected a set of 143 histologically-normal breast tissues derived from patients harboring breast cancer who underwent curative mastectomy, as well as a set of 42 invasive ductal carcinomas (IDC) of various histologic grades. All samples were assessed for global gene expression differences using microarray analysis. For the purpose of this study we defined normal breast tissue to include histologically normal and benign lesions. Here we report the discovery of a “malignancy-risk” gene signature that may portend risk of breast cancer development in benign, but molecularly-abnormal, breast tissue. Pathway analysis showed that the malignancy-risk signature had a dramatic enrichment for genes with proliferative function, but appears to be independent of ER, PR, and HER2 status. The signature was validated by RT-PCR, with a high correlation (Pearson correlation=0.95 with p<0.0001) with microarray data. These results suggest a predictive role for the malignancy-risk signature in normal breast tissue. Proliferative biology dominates the earliest stages of tumor development.
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影响因子：
168.9
作者：
Huang, E;Cheng, SH;Huang, AT
通讯作者：
Huang, AT
影响因子：
5.2
作者：
Botti, C;Pescatore, B;Cianciulli, AM
通讯作者：
Cianciulli, AM
影响因子：
9.6
作者：
Fredriksson, I;Liljegren, G;Frisell, J
通讯作者：
Frisell, J
影响因子：
3.3
作者：
ROBBINS, P;PINDER, S;ELSTON, C
通讯作者：
ELSTON, C
DOI：
10.1073/pnas.0931261100
发表时间：
2003-05-13
影响因子：
11.1
作者：
Ma, XJ;Salunga, R;Sgroi, DC
通讯作者：
Sgroi, DC