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Expression of EEF1A1 Is Associated with Prognosis of Patients with Colon Adenocarcinoma.

ABSTRACT: BACKGROUND:The prognostic role of the translational factor, elongation factor-1 alpha 1 (EEF1A1), in colon cancer is unclear. OBJECTIVES:The present study aimed to investigate the expression of EEF1A in tissues obtained from patients with stage II and III colon cancer and analyze its association with patient prognosis. METHODS:A total of 281 patients with colon cancer who underwent curative resection were analyzed according to EEF1A1 expression. RESULTS:The five-year overall survival in the high-EEF1A1 group was 87.7%, whereas it was 65.6% in the low-EEF1A1 expression group (hazard ratio (HR) 2.47, 95% confidence interval (CI) 1.38-4.44, p = 0.002). The five-year disease-free survival of patients with high EEF1A1 expression was 82.5%, which was longer than the rate of 55.4% observed for patients with low EEF1A1 expression (HR 2.94, 95% CI 1.72-5.04, p < 0.001). Univariate Cox regression analysis indicated that age, preoperative carcinoembryonic antigen level, adjuvant treatment, total number of metastatic lymph nodes, and EEF1A1 expression level were significant prognostic factors for death. In multivariate analysis, expression of EEF1A1 was an independent prognostic factor associated with death (HR 3.01, 95% CI 1.636-5.543, p < 0.001). EEF1A1 expression was also an independent prognostic factor for disease-free survival in multivariate analysis (HR 2.54, 95% CI 1.459-4.434, p < 0.001). CONCLUSIONS:Our study demonstrated that high expression of EEF1A1 has a favorable prognostic effect on patients with colon adenocarcinoma.

SUBMITTER: Joung EK

PROVIDER: S-EPMC6912729 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Expression of <i>EEF1A1</i> Is Associated with Prognosis of Patients with Colon Adenocarcinoma.

Joung Eun Kyo EK Kim Jiyoung J Yoon Nara N Maeng Lee-So LS Kim Ji Hoon JH Park Sungsoo S Kang Keunsoo K Kim Jeong Seon JS Ahn Young-Ho YH Ko Yoon Ho YH Byun Jae Ho JH Hong Ji Hyung JH

Journal of clinical medicine 20191107 11

<h4>Background</h4>The prognostic role of the translational factor, elongation factor-1 alpha 1 (EEF1A1), in colon cancer is unclear.<h4>Objectives</h4>The present study aimed to investigate the expression of EEF1A in tissues obtained from patients with stage II and III colon cancer and analyze its association with patient prognosis.<h4>Methods</h4>A total of 281 patients with colon cancer who underwent curative resection were analyzed according to EEF1A1 expression.<h4>Results</h4>The five-year ...[more]

PMID: 31703307

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Project description:ContextMicroRNAs have potential as diagnostic biomarkers and therapeutic targets in cancer. No study has evaluated the association between microRNA expression patterns and colon cancer prognosis or therapeutic outcome.ObjectiveTo identify microRNA expression patterns associated with colon adenocarcinomas, prognosis, or therapeutic outcome.Design, setting, and patientsMicroRNA microarray expression profiling of tumors and paired nontumorous tissues was performed on a US test cohort of 84 patients with incident colon adenocarcinoma, recruited between 1993 and 2002. We evaluated associations with tumor status, TNM staging, survival prognosis, and response to adjuvant chemotherapy. Associations were validated in a second, independent Chinese cohort of 113 patients recruited between 1991 and 2000, using quantitative reverse transcription polymerase chain reaction assays. The final date of follow-up was December 31, 2005, for the Maryland cohort and August 16, 2004, for the Hong Kong cohort.Main outcome measuresMicroRNAs that were differentially expressed in tumors and microRNA expression patterns associated with survival using cancer-specific death as the end point. RESULTS Thirty-seven microRNAs were differentially expressed in tumors from the test cohort. Selected for validation were miR-20a, miR-21, miR-106a, miR-181b, and miR-203, and all 5 were enriched in tumors from the validation cohort (P < .001). Higher miR-21 expression was present in adenomas (P = .006) and in tumors with more advanced TNM staging (P < .001). In situ hybridization demonstrated miR-21 to be expressed at high levels in colonic carcinoma cells. The 5-year cancer-specific survival rate was 57.5% for the Maryland cohort and was 49.5% for the Hong Kong cohort. High miR-21 expression was associated with poor survival in both the training (hazard ratio, 2.5; 95% confidence interval, 1.2-5.2) and validation cohorts (hazard ratio, 2.4; 95% confidence interval, 1.4-3.9), independent of clinical covariates, including TNM staging, and was associated with a poor therapeutic outcome.ConclusionsExpression patterns of microRNAs are systematically altered in colon adenocarcinomas. High miR-21 expression is associated with poor survival and poor therapeutic outcome.

Project description:BackgroundColon adenocarcinoma (COAD) is the most common colon cancer exhibiting high mortality. Due to their association with cancer progression, long noncoding RNAs (lncRNAs) are now being used as prognostic biomarkers. In the present study, we used relevant clinical information and expression profiles of lncRNAs originating from The Cancer Genome Atlas database, aiming to construct a prognostic lncRNA signature to estimate the prognosis of patients.MethodsThe samples were randomly spilt into training and validation cohorts. In the training cohort, prognosis-related lncRNAs were selected from differentially expressed lncRNAs using the univariate Cox analysis. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox analysis were employed for identifying prognostic lncRNAs. The prognostic signature was constructed by these lncRNAs.ResultsThe prognostic model was able to calculate each COAD patient's risk score and split the patients into groups of low and high risks. Compared to the low-risk group, the high-risk group had significant poor prognosis. Next, the prognostic signature was validated in the validation, as well as all cohorts. The receiver operating characteristic (ROC) curve and c-index were determined in all cohorts. Moreover, these prognostic lncRNA signatures were combined with clinicopathological risk factors to construct a nomogram for predicting the prognosis of COAD in the clinic. Finally, seven lncRNAs (CTC-273B12.10, AC009404.2, AC073283.7, RP11-167H9.4, AC007879.7, RP4-816N1.7, and RP11-400N13.2) were identified and validated by different cohorts. The Kyoto Encyclopedia of Genes and Genomes analysis of the mRNAs co-expressed with the seven prognostic lncRNAs suggested four significantly upregulated pathways, which were AGE-RAGE, focal adhesion, ECM-receptor interaction, and PI3K/Akt signaling pathways.ConclusionThus, our study verified that the seven lncRNAs mentioned can be used as biomarkers to predict the prognosis of COAD patients and design personalized treatments.

Project description:Colon adenocarcinoma (COAD) is one of the most common malignant tumors and has high migration and invasion capacity. In this study, we attempted to establish a multigene signature for predicting the prognosis of COAD patients. Weighted gene co-expression network analysis and differential gene expression analysis methods were first applied to identify differentially co-expressed genes between COAD tissues and normal tissues from the Cancer Genome Atlas (TCGA)-COAD dataset and GSE39582 dataset, and a total of 309 overlapping genes were screened out. Then, our study employed TCGA-COAD cohort as the training dataset and an independent cohort by merging the GES39582 and GSE17536 datasets as the testing dataset. After univariate and multivariate Cox regression analyses were performed for these overlapping genes and overall survival (OS) of COAD patients in the training dataset, a 13-gene signature was constructed to divide COAD patients into high- and low-risk subgroups with significantly different OS. The testing dataset exhibited the same results utilizing the same predictive signature. The area under the curve of receiver operating characteristic analysis for predicting OS in the training and testing datasets were 0.789 and 0.868, respectively, which revealed the enhanced predictive power of the signature. Multivariate Cox regression analysis further suggested that the 13-gene signature could independently predict OS. Among the 13 prognostic genes, NAT1 and NAT2 were downregulated with deep deletions in tumor tissues in multiple COAD cohorts and exhibited significant correlations with poorer OS based on the GEPIA database. Notably, NAT1 and NAT2 expression levels were positively correlated with infiltrating levels of CD8+ T cells and dendritic cells, exhibiting a foundation for further research investigating the antitumor immune roles played by NAT1 and NAT2 in COAD. Taken together, the results of our study showed that the 13-gene signature could efficiently predict OS and that NAT1 and NAT2 could function as biomarkers for prognosis and the immune response in COAD.

Project description:Background: Epithelial-mesenchymal transition (EMT) plays an important role in the invasion and migration during cancer metastasis. Wnt3a is one of the ligands in canonical Wnt/?-catenin signaling pathway, which contributes to the carcinogenesis and progression of lung cancer cell lines. The aim of this study was to evaluate the association between Wnt3a and EMT-related proteins (E-cadherin and N-cadherin), and to further investigate its impact on prognosis of lung adenocarcinoma patients. Methods: A total of 147 lung adenocarcinoma patients were included and their clinicopathological characteristics were collected in this retrospective study. The expression levels of Wnt3a, E-cadherin and N-cadherin in post-surgery cancerous and adjacent normal tissues were assessed by immunohistochemistry. The association between Wnt3a and EMT-related proteins and their prognostic values were systematically evaluated. HCC827 and PC9 cell lines were treated with Wnt3a to detect the expression of EMT-related and Wnt/?-catenin signaling-associated proteins, as well as the in vitro migration and invasion abilities. Results: High Wnt3a expression level was significantly associated with low E-cadherin (P<0.001) and high N-cadherin (P<0.001) expression levels in lung adenocarcinoma tissues. Besides, high Wnt3a level predicted poorer lung adenocarcinoma survival by univariate Cox analysis (P=0.001), while the multivariate result was not significant (P=0.355). Subgroup analysis suggested that the prognostic value of Wnt3a expression level was significant in stage T1-T2 (log rank P=0.003) and stage N0 (log rank P=0.031) patients. The multivariate Cox analysis suggested N-cadherin was an independent prognostic factor for lung adenocarcinoma patients (P=0.012). After including these markers into a nomogram, the Harrell's C-index of the nomogram was 0.755. The decision-curve analysis of our nomogram performed net benefit at the threshold probability from 21.6% to 82.0%, and the current model had a better prognostic value than TNM-classification with a lower Akaike information criterion (AIC) value of 166.54. In vitro experiments suggested that Wnt3a could regulate EMT-related proteins and promotes in vitro invasion and migration abilities. Conclusions: Wnt3a could regulate EMT-related proteins and promote the migration and invasion process of lung adenocarcinoma. Although its value as an independent prognostic factor was limited, the combined model suggested good prognostic performance for lung adenocarcinoma patients.

Project description:BackgroundColon adenocarcinoma (COAD) is a highly heterogeneous disease, thus making prognostic predictions uniquely challenging. Metabolic reprogramming is emerging as a novel cancer hallmark that may serve as the basis for more effective prognosis strategies.MethodsThe mRNA expression profiles and relevant clinical information of COAD patients were downloaded from public resources. The least absolute shrinkage and selection operator (LASSO) Cox regression model was exploited to establish a prognostic model, which was performed to gain risk scores for multiple genes in The Cancer Genome Atlas (TCGA) COAD patients and validated in GSE39582 cohort. A forest plot and nomogram were constructed to visualize the data. The clinical nomogram was calibrated using a calibration curve coupled with decision curve analysis (DCA). The association between the model genes' expression and six types of infiltrating immunocytes was evaluated. Apoptosis, cell cycle assays and cell transfection experiments were performed.ResultsUnivariate Cox regression analysis results indicated that ten differentially expressed genes (DEGs) were related with disease-free survival (DFS) (P-value< 0.01). A four-gene signature was developed to classify patients into high- and low-risk groups. And patients with high-risk exhibited obviously lower DFS in the training and validation cohorts (P < 0.05). The risk score was an independent parameter of the multivariate Cox regression analyses of DFS in the training cohort (HR > 1, P-value< 0.001). The same findings for overall survival (OS) were obtained GO enrichment analysis revealed several metabolic pathways with significant DEGs enrichment, G1/S transition of mitotic cell cycle, CD8+ T-cells and B-cells may be significantly associated with COAD in DFS and OS. These findings demonstrate that si-FUT1 inhibited cell migration and facilitated apoptosis in COAD.ConclusionThis research reveals that a novel metabolic gene signature could be used to evaluate the prognosis of COAD, and targeting metabolic pathways may serve as a therapeutic alternative.

Dataset Information

Expression of EEF1A1 Is Associated with Prognosis of Patients with Colon Adenocarcinoma.

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Expression of <i>EEF1A1</i> Is Associated with Prognosis of Patients with Colon Adenocarcinoma.

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