Characterization of the Expression of the RNA Binding Protein eIF4G1 and Its Clinicopathological Correlation with Serous Ovarian Cancer

Background Ovarian cancer is the most lethal type of malignant tumor in gynecological cancers and is associated with a high percentage of late diagnosis and chemotherapy resistance. Thus, it is urgent to identify a tumor marker or a molecular target that allows early detection and effective treatment. RNA-binding proteins (RBPs) are crucial in various cellular processes at the post-transcriptional level. The eukaryotic translation initiation factor 4 gamma, 1(eIF4G1), an RNA-binding protein, facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. However, little is known regarding the characteristics of eIF4G1 expression and its clinical significance in ovarian cancer. Therefore, we propose to investigate the expression and clinicopathological significance of eIF4G1 in ovarian cancer patients. Methods We performed Real-time PCR in 40 fresh serous ovarian cancer tissues and 27 normal ovarian surface epithelial cell specimens to assess eIF4G1mRNA expression. Immunohistochemistry (IHC) was used to examine the expression of eIF4G1 at the protein level in 134 patients with serous ovarian cancer and 18 normal ovarian tissues. Statistical analysis was conducted to determine the correlation of the eIF4G1 protein levels with the clinicopathological characteristics and prognosis in ovarian cancer. Results The expression of eIF4G1 was upregulated in serous ovarian cancer tissues at both the mRNA (P = 0.0375) and the protein (P = 0.0007) levels. The eIF4G1 expression was significantly correlated with the clinical tumor stage (P = 0.0004) and omentum metastasis (P = 0.024). Moreover, patients with low eIF4G1 protein expression had a longer overall survival time (P = 0.026). Conclusions These data revealed that eIF4G1 is markedly expressed in serous ovarian cancer and that upregulation of the eIF4G1 protein expression is significantly associated with an advanced tumor stage. Besides, the patients with lower expression of eIF4G1 tend to have a longer overall survival time. Thus, eIF4G1 may contribute to the occurrence and metastasis of ovarian cancer and can serve as a potential therapeutic target for the treatment of ovarian cancer.

[1]  A. Jemal,et al.  Cancer statistics in China, 2015 , 2016, CA: a cancer journal for clinicians.

[2]  David Holmes,et al.  Ovarian cancer: beyond resistance , 2015, Nature.

[3]  E. Papadopoulos,et al.  Molecular mechanism of the dual activity of 4EGI-1: Dissociating eIF4G from eIF4E but stabilizing the binding of unphosphorylated 4E-BP1 , 2015, Proceedings of the National Academy of Sciences.

[4]  Kirsten L. Frieda,et al.  Factor-dependent processivity in human eIF4A DEAD-box helicase , 2015, Science.

[5]  Xiangdong Fang,et al.  Insulin-like growth factor binding protein 5 (IGFBP5) functions as a tumor suppressor in human melanoma cells , 2015, Oncotarget.

[6]  M. Lishner,et al.  eIF4E and eIF4GI have distinct and differential imprints on multiple myeloma's proteome and signaling , 2015, Oncotarget.

[7]  M. Lucchi,et al.  Expression status of candidate genes in mesothelioma tissues and cell lines. , 2015, Mutation research.

[8]  M. Lishner,et al.  Targeting eIF4GI translation initiation factor affords an attractive therapeutic strategy in multiple myeloma. , 2014, Cellular signalling.

[9]  G. Ke,et al.  Decreased Expression of EIF4A1 After Preoperative Brachytherapy Predicts Better Tumor-Specific Survival in Cervical Cancer , 2014, International Journal of Gynecologic Cancer.

[10]  P. Schirmacher,et al.  Insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1) is an important protumorigenic factor in hepatocellular carcinoma , 2014, Hepatology.

[11]  W. Lu,et al.  The tumor suppressing effects of QKI-5 in prostate cancer , 2014, Cancer biology & therapy.

[12]  A. Jemal,et al.  Cancer statistics, 2014 , 2014, CA: a cancer journal for clinicians.

[13]  Jinsong Liu,et al.  TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment. , 2013, Cancer research.

[14]  K. Neugebauer,et al.  How cells get the message: dynamic assembly and function of mRNA–protein complexes , 2013, Nature Reviews Genetics.

[15]  Jiri Zavadil,et al.  DNA damage and eIF4G1 in breast cancer cells reprogram translation for survival and DNA repair mRNAs , 2012, Proceedings of the National Academy of Sciences.

[16]  Norman E. Davey,et al.  Insights into RNA Biology from an Atlas of Mammalian mRNA-Binding Proteins , 2012, Cell.

[17]  Jon R Lorsch,et al.  A mechanistic overview of translation initiation in eukaryotes , 2012, Nature Structural &Molecular Biology.

[18]  Michael K. Hutchinson,et al.  Translation initiator EIF4G1 mutations in familial Parkinson disease. , 2011, American journal of human genetics.

[19]  R. Jackson,et al.  The mechanism of eukaryotic translation initiation and principles of its regulation , 2010, Nature Reviews Molecular Cell Biology.

[20]  Guodong Yang,et al.  RNA-binding protein quaking, a critical regulator of colon epithelial differentiation and a suppressor of colon cancer. , 2010, Gastroenterology.

[21]  Donny D. Licatalosi,et al.  RNA processing and its regulation: global insights into biological networks , 2010, Nature Reviews Genetics.

[22]  W. Wong,et al.  A gene signature predictive for outcome in advanced ovarian cancer identifies a survival factor: microfibril-associated glycoprotein 2. , 2009, Cancer cell.

[23]  S. Ko,et al.  Inhibition of Ovarian Cancer Growth by a Tumor-Targeting Peptide That Binds Eukaryotic Translation Initiation Factor 4E , 2009, Clinical Cancer Research.

[24]  P. Levine,et al.  Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer , 2009, Nature Cell Biology.

[25]  Pamela A Silver,et al.  Systems perspectives on mRNA processing , 2007, Cell Research.

[26]  L. Penalva,et al.  Post-Transcription Meets Post-Genomic: The Saga of RNA Binding Proteins in a New Era , 2006, RNA biology.

[27]  J. Darlix,et al.  Conducting the initiation of protein synthesis: the role of eIF4G , 2003, Biology of the cell.

[28]  E. Meese,et al.  Overexpression of the eukaryotic translation initiation factor 4G (eIF4G‐1) in squamous cell lung carcinoma , 2002, International journal of cancer.

[29]  G. Dreyfuss,et al.  Messenger-RNA-binding proteins and the messages they carry , 2002, Nature Reviews Molecular Cell Biology.

[30]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[31]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.