title: EIF4EBP1 overexpression is associated with poor survival and disease progression in patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  EIF4EBP1 acts as a crucial effector in mTOR signaling pathway. Studies have suggested that EIF4EBP1 plays a critical role in carcinogenesis. However, the clinical significance and biological role of EIF4EBP1 in hepatocellular carcinoma (HCC) have not been elucidated. Therefore, we aimed to investigate the clinical significance of EIF4EBP1 in HCC.
  
  
  METHODS
  Total 128 cases of HCCs were included in this study. EIF4EBP1 expression in HCC tissues was detected by qRT-PCR, Western blot and immunohistochemistry, respectively. Then the relationships between EIF4EBP1 expression and clinical features as well as survival were analyzed.
  
  
  RESULTS
  The expression level of EIF4EBP1 mRNA is significantly higher in 60% (24/40) of fresh HCC tissues than that in the matched adjacent nontumor liver (NCL) tissues (P = 0.044). Similarly, EIF4EBP1 protein is notably upregulated in 8 HCC tissues (randomly selected from the 40 HCCs) measured by Western blot and is significantly increased in another 88 paraffin-embedded HCCs (53%, 47/88) by immunohistochemistry compared with the matched NCLs (P < 0.001). EIF4EBP1 protein expression in HCC tissues is significantly correlated with serum AFP (P = 0.003) and marginally significantly associated with pathological grade (P = 0.085), tumor number (P = 0.084), tumor embolus (P = 0.084) and capsulation (P = 0.073). Patients with higher EIF4EBP1 protein expression have a much worse 5-year overall survival (40.3% vs 73.6%) and 5-year disease-free survival (33.0% vs 49.0%) than those with low expression. Furthermore, Cox regression analysis shows that EIF4EBP1 protein is an independent prognostic factor for overall survival (HR, 2.285; 95% CI, 1.154-4.527; P = 0.018) and disease-free survival (HR, 1.901; 95% CI, 1.067-3.386; P = 0.029) in HCC patients.
  
  
  CONCLUSIONS
  Our results demonstrate for the first time that EIF4EBP1 mRNA and protein are markedly up-regulated in HCC tissues, and the protein overexpression is significantly associated with poor survival and progression, which provide a potential new prognostic marker and therapeutic target for HCC patients.
authors: State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China; National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors: Yin-Lian
authors: YL
authors: Cha
authors: State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China; National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors: Pin-Dong
authors: PD
authors: Li
authors: State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China; National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors: Lin-Jing
authors: LJ
authors: Yuan
authors: State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China; National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors: Mei-Yin
authors: MY
authors: Zhang
authors: Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors: Yao-Jun
authors: YJ
authors: Zhang
authors: Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors: Hui-Lan
authors: HL
authors: Rao
authors: Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors: Hui-Zhong
authors: HZ
authors: Zhang
authors: Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey, United States of America.
authors: X F Steven
authors: XF
authors: Zheng
authors: State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China; National Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
authors: Hui-Yun
authors: HY
authors: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*; D018797:Cell Cycle Proteins; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D055815:Young Adult; D000509:alpha-Fetoproteins / Q000032:analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; D012333:RNA, Messenger; D000509:alpha-Fetoproteins