Overexpression of eIF4E in colorectal cancer patients is associated with liver metastasis
Authors Xu T, Zong Y, Peng L, Kong S, Zhou M, Zou J, Liu J, Miao R, Sun X, Li L
Received 15 October 2015
Accepted for publication 8 December 2015
Published 19 February 2016 Volume 2016:9 Pages 815—822
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Yuanzhong Wang
Peer reviewer comments 3
Editor who approved publication: Professor Daniele Santini
Tao Xu,1 Yuanyuan Zong,2 Lipan Peng,1 Shuai Kong,1 Mingliang Zhou,1 Jianqiang Zou,1 Jinglei Liu,1 Ruizheng Miao,1 Xichao Sun,2 Leping Li1
1Department of Gastrointestinal Surgery, 2Department of Pathology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China
Purpose: Liver metastasis is one of the leading causes of death in colorectal cancer (CRC) patients. The present study aimed to evaluate the value of eIF4E as a prognostic marker of colorectal liver metastasis (CLM) and identify the functional role of eIF4E in CRC metastasis.
Patients and methods: The expression level of eIF4E in CRC tissues was analyzed by immunohistochemical staining and Western blot. Expression of eIF4E in CRC cell lines was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot. Cell Counting Kit-8 (CCK-8) and Transwell assays were performed to assess the effects of eIF4E on cell proliferation, migration, and invasion. Western blot was further used to investigate the mechanism of eIF4E in tumor metastasis.
Results: The upregulation frequency of eIF4E in the CLM group (82.5%) was higher than that in the non-CLM group (65.0%). Of the 80 patients recruited for the follow-up study, 23 were in the low eIF4E group (ratio of tumor to nontumor tissue < twofold), and 57 were in the high eIF4E group (ratio of tumor to nontumor tissue ≥twofold). In addition, the group exhibiting high eIF4E expression had a higher rate of liver metastasis (47.4%) than the group exhibiting low eIF4E expression (13.0%). In CRC cell lines, the expression of eIF4E was higher than in the normal cells. In vitro functional studies indicated that eIF4E knockdown inhibited the proliferation, migration, and invasion of Lovo and SW480 cells, and suppressed the expression of cyclin D1, VEGF, MMP-2, and MMP-9.
Conclusion: The results of the present study indicated that high eIF4E levels in CRC patients predicted a high risk of liver metastasis. Knockdown of eIF4E inhibited CRC cell metastasis in part through regulating the expression of cyclin D1, VEGF, MMP-2, and MMP-9.
Keywords: eIF4E, colorectal cancer, liver metastasis, functional study
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