Evaluation of biological pathways involved in chemotherapy response in breast cancer.
Evaluation of biological pathways involved in chemotherapy response in breast cancer.
复制标题
评估乳腺癌化学疗法反应的生物途径。
DOI：
10.1186/bcr2088
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发表时间：
2008
影响因子：
7.4
通讯作者：
Pusztai, Lajos
中科院分区：
文献类型：
--
作者：
Tordai, Attila;Wang, Jing;Andre, Fabrice;Liedtke, Cornelia;Yan, Kai;Sotiriou, Christos;Hortobagyi, Gabriel N.;Symmans, W. Fraser;Pusztai, Lajos
我们的目标是分别研究雌激素受体阳性（ER+）和ER阴性（ER-）乳腺肿瘤的生物学途径与化疗反应之间的关系。将包括852个预定义基因集的基因集富集分析应用于来自51个ER-和82个ER+乳腺肿瘤的基因表达数据，这些肿瘤均接受了术前紫杉醇、5-氟尿嘧啶、多柔比星和环磷酰胺化疗。27例（53%）ER-和7例（9%）ER+患者对治疗有病理学完全缓解（pCR）。在ER肿瘤中，增殖基因特征（假发现率[FDR] q = 0.1）、基因组分级指数（FDR q = 0.044）和E2 F3途径特征（FDR q = 0.22，P = 0.07）在pCR组中富集。在ER+肿瘤中，增殖特征（FDR q = 0.001）和基因组分级指数（FDR q = 0.015）在pCR病例中也显著富集。Ki 67表达作为增殖的单基因标记物，不提供与整个增殖标记相同的信息。ER相关基因集（FDR q = 0.03）和突变型p53基因签名（FDR q = 0.0019）在具有残留癌的ER+肿瘤中富集。增殖和基因组分级相关的基因特征与ER-和ER+乳腺肿瘤的化疗敏感性相关。参与E2 F3通路的基因与ER肿瘤的化疗敏感性相关。突变型p53特征和ER相关基因的表达仅与ER+乳腺肿瘤对化疗的敏感性降低相关。
Our goal was to examine the association between biological pathways and response to chemotherapy in estrogen receptor-positive (ER+) and ER-negative (ER-) breast tumors separately. Gene set enrichment analysis including 852 predefined gene sets was applied to gene expression data from 51 ER- and 82 ER+ breast tumors that were all treated with a preoperative paclitaxel, 5-fluoruracil, doxorubicin, and cyclophosphamide chemotherapy. Twenty-seven (53%) ER- and 7 (9%) ER+ patients had pathologic complete response (pCR) to therapy. Among the ER- tumors, a proliferation gene signature (false discovery rate [FDR] q = 0.1), the genomic grade index (FDR q = 0.044), and the E2F3 pathway signature (FDR q = 0.22, P = 0.07) were enriched in the pCR group. Among the ER+ tumors, the proliferation signature (FDR q = 0.001) and the genomic grade index (FDR q = 0.015) were also significantly enriched in cases with pCR. Ki67 expression, as single gene marker of proliferation, did not provide the same information as the entire proliferation signature. An ER-associated gene set (FDR q = 0.03) and a mutant p53 gene signature (FDR q = 0.0019) were enriched in ER+ tumors with residual cancer. Proliferation- and genomic grade-related gene signatures are associated with chemotherapy sensitivity in both ER- and ER+ breast tumors. Genes involved in the E2F3 pathway are associated with chemotherapy sensitivity among ER- tumors. The mutant p53 signature and expression of ER-related genes were associated with lower sensitivity to chemotherapy in ER+ breast tumors only.
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影响因子：
168.9
作者：
Wang, YX;Klijn, JGM;Foekens, JA
通讯作者：
Foekens, JA
影响因子：
45.3
作者：
Kaufmann, M;von Minckwitz, G;Senn, HJ
通讯作者：
Senn, HJ
DOI：
10.1111/1467-9868.00346
发表时间：
2002-01-01
影响因子：
5.8
作者：
Storey, JD
通讯作者：
Storey, JD
影响因子：
50.3
作者：
Szakács, G;Annereau, JP;Gottesman, MM
通讯作者：
Gottesman, MM
影响因子：
6.2
作者：
Symmans, WF;Ayers, M;Pusztai, L
通讯作者：
Pusztai, L