title: Overexpression of eukaryotic translation initiation factor 5A2 (EIF5A2) correlates with cell aggressiveness and poor survival in gastric cancer.
abstract: Eukaryotic translation initiation factor 5A2 (EIF5A2) plays an important role in tumor progression and prognosis evaluation. However, little information is available about its potential role in gastric cancer. This study aimed to investigate the function of EIF5A2 in tumor progression and its potential mechanisms. EIF5A2 expression was measured in human gastric cancer cell lines, the immortalized gastric mucosal epithelial cell line (GES-1) and human gastric cancer tissues and knocked down by RNA interference or upregulated by EIF5A2 plasmid transfection. Cell proliferation, migration and invasion were assessed in vitro. The downstream targets of EIF5A2 were examined by western blotting. EIF5A2 and its potential target metastasis-associated protein 1 (MTA1) expression were examined in 160 pairs of human gastric cancer and adjacent non-tumor specimens using immunohistochemistry (IHC) staining, and its correlation with clinicopathological features and survival was investigated. Knockdown of EIF5A2 or MTA1 caused an apparent suppression of HGC27 cell proliferation, migration and invasion. After knockdown of EIF5A2 in HGC27 cells, E-cadherin levels were upregulated and vimentin, cyclin D1, cyclin D3, C-MYC and MTA1 levels were downregulated. Upregulation of EIF5A2 in MKN45 cells resulted in the converse. IHC results showed a positive correlation between EIF5A2 and MTA1 expression in gastric cancers (P<0.001). Both EIF5A2 and MTA1 overexpression were correlated with pT stage (P=0.018 and P=0.042), pN stage (P=0.037 and P=0.020) and lymphovascular invasion (P=0.016 and P=0.044). EIF5A2 or MTA1 overexpression was significantly associated with poor overall survival and disease-free survival (All P<0.05). Multivariate analyses identified EIF5A2 as an independent predictor for both overall survival (P=0.012) and disease-free survival (P=0.008) in gastric cancer patients. Our findings indicate that EIF5A2 upregulation plays an important oncogenic role in gastric cancer. EIF5A2 may represent a new predictor for poor survival and is a potential therapeutic target for gastric cancer.
authors: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China; Department of Gastrointestinal Surgery, the First Hospital of Wu Han City, Wuhan city, Hubei Provence, China.
authors: Qing-Bin
authors: QB
authors: Meng
authors: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors: Wei-Ming
authors: WM
authors: Kang
authors: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors: Jian-Chun
authors: JC
authors: Yu
authors: Cell Center, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Wuhan city, Beijing, China.
authors: Yu-Qin
authors: YQ
authors: Liu
authors: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors: Zhi-Qiang
authors: ZQ
authors: Ma
authors: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors: Li
authors: L
authors: Zhou
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors: Quan-Cai
authors: QC
authors: Cui
authors: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
authors: Wei-Xun
authors: WX
authors: Zhou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D055786:Gene Knockout Techniques; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010448:Peptide Initiation Factors / Q000235:genetics*; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D015534:Trans-Activators; D047368:Tumor Burden; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D006655:Histone Deacetylases; D010448:Peptide Initiation Factors; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D000097574:Eukaryotic Translation Initiation Factor 5A; C089320:MTA1 protein, human