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Eukaryotic elongation factor-2 kinase expression is an independent prognostic factor in colorectal cancer.

ABSTRACT: BACKGROUND:Prognostication of patients with colorectal cancer (CRC) currently relies on tumor-node-metastasis (TNM) staging but clinical outcomes of patients of the same histoclinical stage are heterogeneous. It is therefore imperative to devise novel molecular tests to stratify CRC patients. Our previous work demonstrated that eukaryotic elongation factor-2 kinase (EEF2K) is a tumor suppressor in CRC. Herein, we investigated EEF2K expression in CRC and determined its relationship with clinicopathological parameters. METHODS:Quantitative RT-PCR and Westerns blots were used to examine EEF2K expression in primary tumor and the adjacent non-tumor tissues of CRC patients (n =?20). Kaplan-Meier curves and Cox regression analysis were used to assess the association between clinical outcomes of CRC patients and EEF2K protein expression determined by immunohistochemistry on tissue microarray (n =?151). RESULTS:EEF2K was significantly downregulated at both mRNA and protein levels in tumors of CRC patients. Univariate Cox regression analysis revealed that CRC patients with high tumor grade, advanced TNM staging and low EEF2K expression were associated with worse overall survival. Multivariate analysis further demonstrated that low EEF2K expression was an independent factor for predicting poorer overall survival in CRC patients (p =?0.014; Hazard ratio?=?2.951; 95% confidence interval: 1.240-7.024). The 5-year survival rate was 82.8% in the EEF2K-high-expression group versus 63.9% in the EEF2K-low-expression group (p =?0.0118). The association of overall survival with EEF2K expression in CRC patients was verified in The Cancer Genome Atlas (TCGA) cohort. CONCLUSIONS:EEF2K is downregulated in CRC and its expression can be employed as a prognostic marker for CRC patients independent of TNM staging.

SUBMITTER: Ng TH

PROVIDER: S-EPMC6607603 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Eukaryotic elongation factor-2 kinase expression is an independent prognostic factor in colorectal cancer.

Ng Tung H TH Sham Kathy W Y KWY Xie Chuan M CM Ng Simon S M SSM To Ka F KF Tong Joanna H M JHM Liu Wing Y Z WYZ Zhang Lin L Chan Matthew T V MTV Wu William K K WKK Cheng Christopher H K CHK

BMC cancer 20190702 1

<h4>Background</h4>Prognostication of patients with colorectal cancer (CRC) currently relies on tumor-node-metastasis (TNM) staging but clinical outcomes of patients of the same histoclinical stage are heterogeneous. It is therefore imperative to devise novel molecular tests to stratify CRC patients. Our previous work demonstrated that eukaryotic elongation factor-2 kinase (EEF2K) is a tumor suppressor in CRC. Herein, we investigated EEF2K expression in CRC and determined its relationship with c ...[more]

PMID: 31266475

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Project description:ATP binding cassette subfamily D member 3 (ABCD3) is a member of the superfamily of ATP-binding cassette (ABC) transporters, which serve crucial roles in the process of tumor cell resistance to chemotherapy. The present study investigated the diagnostic and prognostic capabilities of ABCD3 in colorectal cancer (CRC) by bioinformatics analysis. Gene expression data and corresponding clinical information of patients with CRC were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The results demonstrated that ABCD3 mRNA level was decreased in CRC tissues compared with normal tissues following Wilcoxon test analysis. Furthermore, ABCD3 protein expression was significantly higher in normal colon tissues compared with colon adenocarcinoma tissues according to the Human Protein Atlas. In addition, the area under the Receiver Operating Characteristic curve based on comparison between the tumor and normal groups derived from TCGA and GEO databases demonstrated that the use of ABCD3 mRNA level may be used for the diagnosis of CRC. ABCD3 expression was significantly associated with clinical stage, T stage, and lymph node status following Kruskal-Wallis test or Wilcoxon rank sum test, logistic regression and χ2 test. Furthermore, the results from Kaplan-Meier survival analysis indicated that low ABCD3 mRNA expression had a poorer prognosis value compared with ABCD3 high expression in patients with CRC. In addition, results from univariate Cox regression analysis indicated that ABCD3 mRNA expression was associated with overall survival (OS), and results from multivariate Cox analysis indicated that ABCD3 mRNA expression may be considered an independent prognostic factor from other clinical factors, such as clinical stage, sex and age. The results from Gene Set Enrichment Analysis demonstrated that the ABCD3 high-expression phenotype was differentially enriched in five biological processes, including apoptosis, cell cycle, renal cell carcinoma, thyroid cancer and colorectal cancer. The findings from this study demonstrated that ABCD3 mRNA expression may be considered as a potential diagnostic and prognostic biomarker in patients with CRC. ABCD3 expression levels may participate in the regulation of cell apoptosis and cell cycle. In addition, GSEA analysis identified Kyoto Encyclopaedia of Genes and Genomes pathways for renal cell carcinoma, thyroid cancer and CRC involving ABCD3.

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Eukaryotic elongation factor-2 kinase expression is an independent prognostic factor in colorectal cancer.

Publications

Eukaryotic elongation factor-2 kinase expression is an independent prognostic factor in colorectal cancer.

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