TGF-beta1 genotype and phenotype in breast cancer and their associations with IGFs and patient survival.
TGF-beta1 genotype and phenotype in breast cancer and their associations with IGFs and patient survival.
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DOI：
10.1038/sj.bjc.6604689
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发表时间：
2008-10-21
影响因子：
8.8
通讯作者：
Yu, H.
中科院分区：
文献类型：
--
作者：
Mu, L.;Katsaros, D.;Lu, L.;Preti, M.;Durando, A.;Arisio, R.;Yu, H.
转化生长因子-β（Transforming growth factor-β，TGF-β）介导的信号在乳腺肿瘤的发生发展中起着复杂的作用。本研究旨在分析乳腺肿瘤组织中TGF-β1 T29 C基因型和TGF-β1表型，并探讨其与IGFs及乳腺癌临床特征的关系。从348名乳腺癌患者中收集了新鲜肿瘤样本。分别用TaqMan®和ELISA分析TGF-β1基因型和表型。用ELISA测定肿瘤组织中IGF家族的成员。采用考克斯比例风险回归分析评估TGF-β1与疾病结局的相关性。T29 C基因型为T/T（29%）的患者TGF-β1最高，为707.9 pg mg−1，其次为T/C（49%），657.8 pg mg−1，C/C（22%）基因型，640.8 pg mg−1（P=0.210，T/T vs C/C和C/T）。TGF-β1浓度与雌激素受体、IGF-I、IGF-II和IGFBP-3水平呈正相关。生存分析显示TGF-β1与疾病进展相关，但这种相关性因疾病分期而异。对于早期疾病，与无T/T或低TGF-β 1的患者相比，具有T/T基因型或高TGF-β 1的患者的总生存期较短;校正年龄、分级、组织型和受体状态后，基因型和表型的风险比（HR）分别为3.54（95%CI：1.21-10.40）和2.54（95%CI：1.10-5.89）。然而，对于晚期疾病，这种关联是不同的。T/T基因型与较低的疾病复发风险相关（HR=0.13，95%CI：0.02-1.00），而TGF-β1表型与生存结局之间无相关性。该研究表明TGF-β1在乳腺癌进展中的复杂作用，这支持了体外研究的发现，即TGF-β1对肿瘤生长和转移具有相互矛盾的作用。
Transforming growth factor-β (TGF-β)-mediated signals play complicated roles in the development and progression of breast tumour. The purposes of this study were to analyse the genotype of TGF-β1 at T29C and TGF-β1 phenotype in breast tumours, and to evaluate their associations with IGFs and clinical characteristics of breast cancer. Fresh tumour samples were collected from 348 breast cancer patients. TGF-β1 genotype and phenotype were analysed with TaqMan® and ELISA, respectively. Members of the IGF family in tumour tissue were measured with ELISA. Cox proportional hazards regression analysis was performed to assess the association of TGF-β1 and disease outcomes. Patients with the T/T (29%) genotype at T29C had the highest TGF-β1, 707.9 pg mg−1, followed by the T/C (49%), 657.8 pg mg−1, and C/C (22%) genotypes, 640.8 pg mg−1, (P=0.210, T/T vs C/C and C/T). TGF-β1 concentrations were positively correlated with levels of oestrogen receptor, IGF-I, IGF-II and IGFBP-3. Survival analysis showed TGF-β1 associated with disease progression, but the association differed by disease stage. For early-stage disease, patients with the T/T genotype or high TGF-β1 had shorter overall survival compared to those without T/T or with low TGF-β1; the hazard ratios (HR) were 3.54 (95% CI: 1.21–10.40) for genotype and 2.54 (95% CI: 1.10–5.89) for phenotype after adjusting for age, grade, histotype and receptor status. For late-stage disease, however, the association was different. The T/T genotype was associated with lower risk of disease recurrence (HR=0.13, 95% CI: 0.02–1.00), whereas no association was found between TGF-β1 phenotype and survival outcomes. The study suggests a complex role of TGF-β1 in breast cancer progression, which supports the finding of in vitro studies that TGF-β1 has conflicting effects on tumour growth and metastasis.
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DOI：
10.1196/annals.1386.024
发表时间：
2006-01-01
期刊：
ESTROGENS AND HUMAN DISEASES
影响因子：
--
作者：
Buck, Miriam B.;Knabbe, Cornelius
通讯作者：
Knabbe, Cornelius
影响因子：
8.8
作者：
MURRAY, PA;BARRETTLEE, P;COOMBES, RC
通讯作者：
COOMBES, RC
影响因子：
8.4
作者：
Ladd, A. M. Gonzalez-Zuloeta;Arias-Vasquez, A.;van Duijn, C. M.
通讯作者：
van Duijn, C. M.
DOI：
10.1083/jcb.127.6.2021
发表时间：
1994-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Miettinen PJ;Ebner R;Lopez AR;Derynck R
通讯作者：
Derynck R
DOI：
10.1186/bcr44
发表时间：
2000
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dumont N;Arteaga CL
通讯作者：
Arteaga CL