Dataset Information

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.

SUBMITTER: Cha YL

PROVIDER: S-EPMC4319970 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

EIF4EBP1 overexpression is associated with poor survival and disease progression in patients with hepatocellular carcinoma.

Cha Yin-Lian YL Li Pin-Dong PD Yuan Lin-Jing LJ Zhang Mei-Yin MY Zhang Yao-Jun YJ Rao Hui-Lan HL Zhang Hui-Zhong HZ Zheng X F Steven XF Wang Hui-Yun HY

PloS one 20150206 2

<h4>Objective</h4>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.<h4>Methods</h4>Total 128 cases of HCCs were included in this study. EIF4EBP1 expression in HCC tissues was detected by qRT-PCR, Weste ...[more]

PMID: 25658620

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Project description:PurposeOur research was aimed to identify the expression, clinical value and biological significance of GINS complex subunit 4 (GINS4) in hepatocellular carcinoma (HCC).Materials and methodsGINS4 was initially screened through weighted gene co-expression network analysis (WGCNA). The TCGA, GEO, and TIMER databases were applied for analyzing the GINS4 mRNA expression in HCC. GINS4 protein levels were detected via immunohistochemistry (IHC). Receiver operating characteristic (ROC) curve was applied for estimating the diagnostic significance of GINS4 in HCC. Kaplan-Meier plots, Cox model, and nomogram were used to assess the prognostic performance of GINS4 in HCC. Nomogram validation was conducted through time-dependent ROC and decision curve analysis (DCA). The Wanderer, UALCAN, and DiseaseMeth databases were utilized to identify GINS4 methylation levels in HCC. Genes co-expressed with GINS4 in HCC were estimated through the TCGA, cBioPortal, and GEPIA. GO, KEGG, and GSEA unraveled the possible biological mechanisms of GINS4 in HCC.ResultsWGCNA confirmed that GINS4 was one of hub genes significantly associated with histological grade of HCC. Multiple databases confirmed the significant upregulation of GINS4 in HCC tissues compared with non-tumor controls. IHC analysis of 35 HCC patients demonstrated that overexpressed GINS4 positively correlated with advanced TNM stage and poor pathological differentiation. GINS4 could effectively differentiate HCC cases from healthy individuals, with an AUC of 0.865. Increased GINS4 expression predicted unsatisfactory prognosis in HCC patients, especially in age >60 years, histological grade 1, HBV infection-negative, and occurring relapse subgroup. Nomogram incorporating GINS4 level and TNM stage displayed satisfactory predictive accuracy and clinical utility in predicting HCC prognosis. Upregulated GINS4 exhibited hypomethylated levels in HCC. Functional analysis indicated that GINS4 potentially positively modulated cell cycle and PI3K/AKT/mTOR pathway.ConclusionGINS4 is overexpressed in HCC and is correlated with undesirable survival of HCC patients.

Project description:Hepatocellular carcinoma (HCC) is a common malignant tumor in the clinic. Although there are increasing numbers of available treatment methods, their therapeutic effects are not satisfactory. The clinical indicators commonly used to predict the prognosis of HCC include tumor size, degree of cirrhosis, degree of tumor differentiation and tumor microvascular invasion; however, there are currently no molecular indicators that can predict the prognosis of HCC. Due to the differences in the progression of liver cancer among individuals, there is a growing need for prognostic biomarkers to accurately stratify patients for appropriate risk-adaptive treatment. The DNA topoisomerase 2-? (TOP2A) gene, which is located on human chromosome 17, encodes DNA topoisomerase II?. Previous studies have demonstrated that TOP2A indicates a poor prognosis in patients with various types of tumors, but no such studies are currently available on HCC. By analyzing the differential expression of TOP2A in 50 pairs of tumor and paracancerous tissue samples in The Cancer Genome Atlas (TCGA) database, the present study revealed that the expression of TOP2A was significantly higher in tumor tissue compared with that in paracancerous tissue (P=6.319×10-16). In the collected clinical samples, the mRNA expression levels of TOP2A were significantly upregulated in HCC tumor tissues compared with those in the paracancerous tissues (P=6.40×10-3), suggesting that TOP2A was associated with the occurrence and development of liver cancer. In addition, the associations between TOP2A expression, clinicopathological features and prognosis were analyzed using a multi-center large sample dataset from TCGA database, and the results demonstrated that high expression of TOP2A was associated with a higher T stage, poorer clinical stage and higher histological grade compared with those in patients with low TOP2A expression. High expression of TOP2A was also identified to be associated with a poor prognosis of HCC, particularly in Asian populations. These results suggested that high expression of TOP2A in HCC tissues may be closely associated with tumor progression and metastasis, which may be used as a biological indicator to predict tumor prognosis in clinical practice.

Dataset Information

EIF4EBP1 overexpression is associated with poor survival and disease progression in patients with hepatocellular carcinoma.

Objective

Methods

Results

Conclusions

Publications

EIF4EBP1 overexpression is associated with poor survival and disease progression in patients with hepatocellular carcinoma.

Similar Datasets

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