Expression of 4E-BP1 and phospho-4E-BP1 correlates with the prognosis of patients with clear cell renal carcinoma

0301 basic medicine 4E-BP1 VEGFC ccRCC Neoplasms. Tumors. Oncology. Including cancer and carcinogens PI3K 3. Good health 03 medical and health sciences Cancer Management and Research eIF4E phospho-4E-BP1 RC254-282 Original Research
DOI: 10.2147/cmar.s158547 Publication Date: 2018-06-14T21:39:01Z
ABSTRACT
Eukaryotic translation initiation factor 4E (eIF4E) is a key regulator of protein synthesis. Changes in eIF4E activity disproportionally affect the translation of a subset of oncogenic mRNAs in some cancers.We have assessed the expression levels of vascular endothelial growth factor C (VEGFC), eIF4E, eIF4E-binding proteins (4E-BPs) and phospho-4E-BP1 in clear cell renal carcinoma (ccRCC; n=101) using immunohistochemistry and analyzed the relevant mRNA levels and survival using online databases.The protein levels of VEGFC, an eIF4E-regulated gene, were upregulated in ccRCC tissues compared with adjacent normal renal tissues, indicating an enhanced eIF4E activity in ccRCC. The expression of eIF4E had no significant changes in ccRCC tissues. However, 4E-BP1 and phospho-4E-BP1 were found to be overexpressed in ccRCC tissues (P<0.05), and the high mRNA and protein levels of 4E-BP1 and phospho-4E-BP1 correlated with an unfavorable clinical outcome in ccRCC patients. Meanwhile, the mRNA expression of PIK3CD and PIK3CG were enhanced in ccRCC.From these results, we could infer that the increase in eIF4E activity may be caused by the increased phospho-4E-BP1 level, which was probably due to the activation of phosphoinositide 3-kinase (PI3K) pathway.
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