The prognostic role of TGF-β signaling pathway in breast cancer patients

被引：73
作者：
de Kruijf, E. M. [1 ]
Dekker, T. J. A. [1 ,2 ]
Hawinkels, L. J. A. C. [3 ,4 ]
Putter, H. [5 ]
Smit, V. T. H. B. M. [6 ]
Kroep, J. R. [2 ]
Kuppen, P. J. K. [1 ]
van de Velde, C. J. H. [1 ]
ten Dijke, P. [3 ,4 ,7 ]
Tollenaar, R. A. E. M. [1 ]
Mesker, W. E. [1 ]
机构：
[1] Leiden Univ, Med Ctr, Dept Surg, NL-2300 RC Leiden, Netherlands
[2] Leiden Univ, Med Ctr, Dept Med Oncol, NL-2300 RC Leiden, Netherlands
[3] Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RC Leiden, Netherlands
[4] Leiden Univ, Med Ctr, Ctr Biomed Genet, NL-2300 RC Leiden, Netherlands
[5] Leiden Univ, Med Ctr, Dept Med Stat, NL-2300 RC Leiden, Netherlands
[6] Leiden Univ, Med Ctr, Dept Pathol, NL-2300 RC Leiden, Netherlands
[7] Uppsala Univ, Ludwig Inst Canc Res, Uppsala, Sweden
来源：
ANNALS OF ONCOLOGY | 2013年 / 24卷 / 02期
关键词：
breast cancer; prognosis; p-Smad2; smad4; TGF-beta receptor I; TGF-beta receptor II; GROWTH-FACTOR-BETA; TUMOR-SUPPRESSOR SMAD4; MESENCHYMAL TRANSITION; TRANSFORMING GROWTH-FACTOR-BETA-1; CELL-LINES; RECEPTOR; INDUCTION; METASTASIS; EXPRESSION; TGF-BETA-1;
D O I：
10.1093/annonc/mds333
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
The transforming growth factor-beta (TGF-beta) pathway has dual effects on tumor growth. Seemingly, discordant results have been published on the relation between TGF-beta signaling markers and prognosis in breast cancer. Improved prognostic information for breast cancer patients might be obtained by assessing interactions among TGF-beta signaling biomarkers. The expression of nuclear Smad4, nuclear phosphorylated-Smad2 (p-Smad2), and the membranous expression of TGF-beta receptors I and II (T beta RI and T beta RII) was determined on a tissue microarray of 574 breast carcinomas. Tumors were stratified according to the Smad4 expression in combination with p-Smad2 expression or Smad4 in combination with the expression of both TGF-beta receptors. Tumors with high expression of T beta RII, T beta RI and T beta RII, and p-Smad2 (P = 0.018, 0.005, and 0.022, respectively), and low expression of Smad4 (P = 0.005) had an unfavorable prognosis concerning progression-free survival. Low Smad4 expression combined with high p-Smad2 expression or low expression of Smad4 combined with high expression of both TGF-beta receptors displayed an increased hazard ratio of 3.04 [95% confidence interval (CI) 1.390-6.658] and 2.20 (95% CI 1.464-3.307), respectively, for disease relapse. Combining TGF-beta biomarkers provides prognostic information for patients with stage I-III breast cancer. This can identify patients at increased risk for disease recurrence that might therefore be candidates for additional treatment.
引用
收藏
页码：384 / 390
页数：7
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