Dataset Information

Identifying an Eight-Gene Signature to Optimize Overall Survival Prediction of Esophageal Adenocarcinoma Using Bioinformatics Analysis of ceRNA Network.

ABSTRACT:

Background and aims

Esophageal adenocarcinoma (EAC) patients usually have a poor prognosis without early diagnosis. In this study, we aimed to identify a novel signature to improve the prediction of overall survival (OS) in EAC.

Methods

Eighty-one and 68 samples from The Cancer Genome Atlas (TCGA) and GSE19417 dataset were included for discovery and survival validation, respectively. In the TCGA cohort, a total of 1,811 DEmRNAs, 1,096 DElncRNAs, and 31 DEmiRNAs were identified between EAC and normal esophagus tissues. A mRNA-miRNA-lncRNA ceRNA network of EAC was established, which consisted of 94 DEmRNAs, 13 DEmiRNAs, and 46 DElncRNAs.

Results

In this study, we identified eight genes (UBE2B, LAMP2, B3GNT2, TAF9B, EFNA1, PHF8, PIGA, and NEURL1) which were related to survival in EAC. The independent external microarray data from the Gene Expression Omnibus (GEO) was used to validate these candidate genes. The prognostic ability of the signature was also validated in EAC patients in our hospital. Patients assigned to the high-risk group had a poor overall survival rate compared with the low-risk.

Conclusion

The current study provides novel insights into the mRNA-related ceRNA network in EAC and the eight mRNA biomarkers may be independent prognostic signatures in predicting the survival of EAC patients.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7764560 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Identifying an Eight-Gene Signature to Optimize Overall Survival Prediction of Esophageal Adenocarcinoma Using Bioinformatics Analysis of ceRNA Network.

Wang Yuanyong Y Liang Naixin N Xue Zhiqiang Z Xue Xinying X

OncoTargets and therapy 20201222

<h4>Background and aims</h4>Esophageal adenocarcinoma (EAC) patients usually have a poor prognosis without early diagnosis. In this study, we aimed to identify a novel signature to improve the prediction of overall survival (OS) in EAC.<h4>Methods</h4>Eighty-one and 68 samples from The Cancer Genome Atlas (TCGA) and GSE19417 dataset were included for discovery and survival validation, respectively. In the TCGA cohort, a total of 1,811 DEmRNAs, 1,096 DElncRNAs, and 31 DEmiRNAs were identified bet ...[more]

PMID: 33376353

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Project description:BackgroundLung cancer has become the most common cancer type and caused the most cancer deaths. Lung adenocarcinoma (LUAD) is one of the major types of lung cancer. Accumulating evidence suggests the tumor microenvironment is correlated with the tumor progress and the patient's outcome. This study aimed to establish a gene signature based on tumor microenvironment that can predict patients' outcomes for LUAD.MethodsDataset TCGA-LUAD, downloaded from the TCGA portal, were taken as training cohort, and dataset GSE72094, obtained from the GEO database, was set as validation cohort. In the training cohort, ESTIMATE algorithm was applied to find intersection differentially expressed genes (DEGs) among tumor microenvironment. Kaplan-Meier analysis and univariate Cox regression model were performed on intersection DEGs to preliminarily screen prognostic genes. Besides, the LASSO Cox regression model was implemented to build a multi-gene signature, which was then validated in the validation cohorts through Kaplan-Meier, Cox, and receiver operating characteristic curve (ROC) analyses. In addition, the correlation between tumor mutational burden (TMB) and risk score was evaluated by Spearman test. GSEA and immune infiltrating analyses were conducted for understanding function annotation and the role of the signature in the tumor microenvironment.ResultsAn eight-gene signature was built, and it was examined by Kaplan-Meier analysis, revealing that a significant overall survival difference was seen. The eight-gene signature was further proven to be independent of other clinico-pathologic parameters via the Cox regression analyses. Moreover, the ROC analysis demonstrated that this signature owned a better predictive power of LUAD prognosis. The eight-gene signature was correlated with TMB. Furthermore, GSEA and immune infiltrating analyses showed that the exact pathways related to the characteristics of eight-genes signature, and identified the vital roles of Mast cells resting and B cells naive in the prognosis of the eight-gene signature.ConclusionIdentifying the eight-gene signature (INSL4, SCN7A, STAP1, P2RX1, IKZF3, MS4A1, KLRB1, and ACSM5) could accurately identify patients' prognosis and had close interactions with Mast cells resting and B cells naive, which may provide insight into personalized prognosis prediction and new therapies for LUAD patients.

Project description:Background: Ferroptosis is an iron-dependent programmed cell death process. Recent studies have found that ferroptosis inducers hold promising potential in the treatment of lung adenocarcinoma (LUAD). However, the comprehensive analysis about the prognostic value of ferroptosis-related genes in LUAD remains to be elucidated. Methods: The RNA sequencing data and corresponding clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A total of 259 ferroptosis-related genes were extracted from FerrDb website. The ferroptosis-related prognostic signature was developed by least absolute shrinkage and selection operator (LASSO) Cox regression analysis in TCGA LUAD cohort, and then validated by 5 independent GEO cohorts. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed to identify the difference in biological processes and functions between different risk groups. The expression levels of core prognostic genes were then verified in LUAD samples by immunohistochemistry (IHC) and erastin-treated LUAD cell lines by real-time polymerase chain reaction (PCR). The potential roles of GPX2 and DDIT4 as ferroptosis drivers in LUAD cell line were further confirmed by in vitro experiments. Results: A total of 20 intersecting genes between 70 ferroptosis-related DEGs and 45 potential prognostic genes were obtained for LASSO Cox regression analysis. The ferroptosis-related prognostic signature was developed by 7 core prognostic DEGs, and stratified LUAD patients into two risk groups. Kaplan-Meier analysis showed that the overall survival (OS) of LUAD patients in the high-risk group was significantly worse than that of the low-risk group. External validation of 5 independent GEO cohorts further confirmed that the ferroptosis-related prognostic signature was an ideal biomarker for predicting the survival of LUAD patients. Significant enrichment of fatty acid metabolism and cell cycle-related pathways were found in different risk groups. The expression patterns of 7 core prognostic genes in LUAD and adjacent normal lung tissues were validated by IHC, which was almost consistent with the results from public database. Furthermore, the changes related to cell cycle and ferroptosis after erastin treatment were also validated in LUAD cell lines. In addition, silencing GPX2 or DDIT4 could partially reverse the erastin-induced ferroptosis. Conclusion: In summary, the ferroptosis-related prognostic signature based on 7 core prognostic DEGs indicated superior predictive performance of LUAD patients. Targeting ferroptosis holds potential to be a therapeutic alternative for LUAD.

Dataset Information

Identifying an Eight-Gene Signature to Optimize Overall Survival Prediction of Esophageal Adenocarcinoma Using Bioinformatics Analysis of ceRNA Network.

Background and aims

Methods

Results

Conclusion

Publications

Identifying an Eight-Gene Signature to Optimize Overall Survival Prediction of Esophageal Adenocarcinoma Using Bioinformatics Analysis of ceRNA Network.

Similar Datasets

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