Aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer.
Aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer.
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DOI：
10.1186/bcr3343
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发表时间：
2012-10-26
期刊：
影响因子：
--
通讯作者：
Gonzalez-Angulo A
中科院分区：
文献类型：
--
作者：
Meric-Bernstam F;Chen H;Akcakanat A;Do KA;Lluch A;Hennessy BT;Hortobagyi GN;Mills GB;Gonzalez-Angulo A
翻译起始在癌症中通过增加真核起始因子4 E（eIF 4 E）、eIF 4G、磷酸化eIF 4 E结合蛋白（p4 E-BP 1）和磷酸化核糖体蛋白S6（pS 6）以及减少程序性细胞死亡蛋白4（pdcd 4）（一种翻译抑制剂）而被激活。此外，翻译延伸通过真核延伸因子2（eEF 2）和eEF 2激酶（eEF 2K）的改变而被解除调节。我们试图确定这些翻译畸变与激素受体阳性乳腺癌的临床病理因素和生存结局的关系。原发性肿瘤收集自190例I期至III期激素受体阳性乳腺癌患者。通过反相蛋白阵列评估eIF 4 E、eIF 4G、4 E-BP 1、p4 E-BP 1 T37/46、p4 E-BP 1 S65、p4 E-BP 1 T70、S6、pS 6 S235/236、pS 6 S240/244、pdcd 4、eEF 2和eEF 2K的表达。对无复发生存期（RFS）和总生存期（OS）进行单变量和多变量分析。高eEF 2、S6、pS 6 S240/244、p4 E-BP 1 T70和低pdcd 4与淋巴结阳性显著相关。存活患者的中位随访时间为96个月。高p4 E-BP 1 T36/47、p4 E-BP 1 S65、p4 E-BP 1 T70和4 E-BP 1与更差的RFS相关。在多变量分析中，除了阳性淋巴结外，p4 E-BP 1 S65仍然是RFS的重要预测因子（HR = 1.62，95%CI = 1.13-2.31; P = 0.008）。除年龄外，pS 6 S235/236（HR = 1.73，95% CI = 1.03-2.90，P = 0.039），eEF 2K（HR = 2.19，95% CI = 1.35-3.56，P = 0.002）和pdcd 4（HR = 0.42，95%CI = 0.25-0.70，P = 0.001）与OS相关。eEF 2K和pdcd 4降低与激素受体阳性乳腺癌的预后不良相关，提示其作为预后标志物和治疗靶点的作用。
Translation initiation is activated in cancer through increase in eukaryotic initiation factor 4E (eIF4E), eIF4G, phosphorylated eIF4E-binding protein (p4E-BP1) and phosphorylated ribosomal protein S6 (pS6), and decreased programmed cell death protein 4 (pdcd4), a translational inhibitor. Further, translation elongation is deregulated though alterations in eukaryotic elongation factor 2 (eEF2) and eEF2 kinase (eEF2K). We sought to determine the association of these translational aberrations with clinical-pathologic factors and survival outcomes in hormone receptor-positive breast cancer. Primary tumors were collected from 190 patients with Stage I to III hormone receptor-positive breast cancer. Expression of eIF4E, eIF4G, 4E-BP1, p4E-BP1 T37/46, p4E-BP1 S65, p4E-BP1 T70, S6, pS6 S235/236, pS6 S240/244, pdcd4, eEF2 and eEF2K was assessed by reverse phase protein arrays. Univariable and multivariable analyses for recurrence-free survival (RFS) and overall survival (OS) were performed. High eEF2, S6, pS6 S240/244, p4E-BP1 T70, and low pdcd4 were significantly associated with node positivity. Median follow-up for living patients was 96 months. High p4E-BP1 T36/47, p4E-BP1 S65, p4E-BP1 T70 and 4E-BP1 were associated with worse RFS. High p4E-BP1 T70 and pS6 S235/236, and low pdcd4, were associated with worse OS. In multivariable analysis, in addition to positive nodes, p4E-BP1 S65 remained a significant predictor of RFS (HR = 1.62, 95% CI = 1.13-2.31; P = 0.008). In addition to age, pS6 S235/236 (HR = 1.73, 95% CI = 1.03-2.90, P = 0.039), eEF2K (HR = 2.19, 95% CI = 1.35-3.56, P = 0.002) and pdcd4 (HR = 0.42, 95% CI = 0.25-0.70, P = 0.001) were associated with OS. Increased pS6, p4E-BP1, eEF2K and decreased pdcd4 are associated with poor prognosis in hormone receptor-positive breast cancer, suggesting their role as prognostic markers and therapeutic targets.
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影响因子：
8.8
作者：
Coleman, L. J.;Peter, M. B.;Teall, T. J.;Brannan, R. A.;Hanby, A. M.;Honarpisheh, H.;Shaaban, A. M.;Smith, L.;Speirs, V.;Verghese, E. T.;McElwaine, J. N.;Hughes, T. A.
通讯作者：
Hughes, T. A.
影响因子：
5.7
作者：
Kuznetsov G;Xu Q;Rudolph-Owen L;Tendyke K;Liu J;Towle M;Zhao N;Marsh J;Agoulnik S;Twine N;Parent L;Chen Z;Shie JL;Jiang Y;Zhang H;Du H;Boivin R;Wang Y;Romo D;Littlefield BA
通讯作者：
Littlefield BA
影响因子：
3.8
作者：
Gonzalez-Angulo AM;Hennessy BT;Meric-Bernstam F;Sahin A;Liu W;Ju Z;Carey MS;Myhre S;Speers C;Deng L;Broaddus R;Lluch A;Aparicio S;Brown P;Pusztai L;Symmans WF;Alsner J;Overgaard J;Borresen-Dale AL;Hortobagyi GN;Coombes KR;Mills GB
通讯作者：
Mills GB
影响因子：
56.9
作者：
Dorrello, N. Valerio;Peschiaroli, Angelo;Pagano, Michele
通讯作者：
Pagano, Michele
影响因子：
9
作者：
Li, BDL;McDonald, JC;De Benedetti, A
通讯作者：
De Benedetti, A