aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer畸变在平移监管与激素受体阳性乳腺癌预后不良有关.pdfVIP

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2017-09-11 发布于上海
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aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer畸变在平移监管与激素受体阳性乳腺癌预后不良有关.pdf

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aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer畸变在平移监管与激素受体阳性乳腺癌预后不良有关

Meric-Bernstam et al. Breast Cancer Research 2012, 14:R138 /content/14/5/R138 RESEARCH ARTICLE Open Access Aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer 1* 2 1 3 4 5,6 Funda Meric-Bernstam , Huiqin Chen , Argun Akcakanat , Kim-Anh Do , Ana Lluch , Bryan T Hennessy , Gabriel N Hortobagyi2, Gordon B Mills7 and Ana Maria Gonzalez-Angulo2,7 Abstract Introduction: 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. Methods: 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. Results: 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