Dataset Information

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: Delta-like ligand 3 (DLL3) is one of the NOTCH family of ligands, which plays a pro- or anti-carcinogenic role in some cancers. But the role of DLL3 in colon adenocarcinoma (COAD) has not been studied in depth. Materials and methods: First, we used Kaplan-Meier (K-M) curve to evaluate the effect of DLL3 on the prognosis of COAD in The Cancer Genome Atlas (TCGA), which was further validated in clinical samples for immunohistochemistry. Then we screened for differentially expressed genes (DEGs) of DLL3 by analyzing datasets of COAD samples from Gene Expression Omnibus (GEO) and TCGA. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and Gene Set Enrichment Analysis (GSEA) were conducted to explore the underlying mechanisms of DLL3-related in the development and prognosis of COAD. On the basis of DLL3-related signature genes, a prognostic model and a nomogram were constructed. Finally, CIBERSORT was applied to assess the proportion of immune cell types in COAD sample. Results: Survival analysis showed a significant difference in overall survival between high- and low-expression group (p = 0.0092), with COAD patients in the high-group having poorer 5-year survival rate. Gene functional enrichment analysis revealed that DLL3-related DEGs were mainly enriched in tumor- and immunity-related signaling pathways, containing AMPK pathway and mitophagy-animal. The comparison of COAD tumor and normal, DLL3 high- and low-expression groups by GSEA found that AMPK signaling pathway and mitophagy-animal were inhibited. Nomogram constructed from DLL3-related signature genes had a good predictive effect on the prognosis of COAD. We found the highest correlation between DLL3 and interstitial dendritic cell (iDC), natural killer (NK) cell and Interstitial dendritic cell (Tem). DLL3 was also revealed to be diagnostic for COAD. In clinical sample, we identified higher DLL3 expression in colon cancer tissue than in adjacent control (p < 0.0001) and in metastasis than in primary lesion (p = 0.0056). DLL3 expression was associated with stage and high DLL3 expression was observed to predict poorer overall survival (p = 0.004). Conclusion: It suggested that DLL3 may offer prognostic value and therapeutic potential for individualized treatment of COAD, and that it may has a diagnostic role in COAD.

Dataset Information

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

Publications

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

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