Dataset Information

A two-circular RNA signature as a noninvasive diagnostic biomarker for lung adenocarcinoma.

ABSTRACT: BACKGROUND:Recently, circular RNAs (circRNAs) have been reported to be microRNA sponges and play essential roles in cancer development. This study aimed to evaluate whether circulating circRNAs could be used as diagnostic biomarkers for lung adenocarcinoma (LUAD). METHODS:The Gene Expression Omnibus (GEO) dataset was used to investigate differentially expressed circRNAs (DEcircRNAs) in paired LUAD tissues and adjacent nontumor tissues. The expression levels of the host genes were analyzed in The Cancer Genome Atlas (TCGA)-LUAD dataset, and the prognostic value was assessed using the Kaplan-Meier plotter. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression of candidate circRNAs in the LUAD plasma and cells. The CCK8 assay was used to measure the function of circRNAs in cell proliferation. Competing endogenous RNA (ceRNA) network, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to predict the possible mechanisms and functions of circRNAs in LUAD. RESULTS:Two upregulated and two downregulated circRNAs were identified as candidate circRNAs using bioinformatics analysis. qRT-PCR demonstrated that hsa_circ_0005962 was upregulated in LUAD plasma and cells, whereas hsa_circ_0086414 was downregulated. Receiver operating characteristic (ROC) curve analysis confirmed that a signature comprising the two circRNAs had good diagnostic potential, with an area under the ROC curve (AUC) of 0.81 (P?

SUBMITTER: Liu XX

PROVIDER: S-EPMC6380039 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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A two-circular RNA signature as a noninvasive diagnostic biomarker for lung adenocarcinoma.

Liu Xiao-Xia XX Yang Yi-E YE Liu Xiao X Zhang Meng-Yu MY Li Rui R Yin Yun-Hong YH Qu Yi-Qing YQ

Journal of translational medicine 20190218 1

<h4>Background</h4>Recently, circular RNAs (circRNAs) have been reported to be microRNA sponges and play essential roles in cancer development. This study aimed to evaluate whether circulating circRNAs could be used as diagnostic biomarkers for lung adenocarcinoma (LUAD).<h4>Methods</h4>The Gene Expression Omnibus (GEO) dataset was used to investigate differentially expressed circRNAs (DEcircRNAs) in paired LUAD tissues and adjacent nontumor tissues. The expression levels of the host genes were ...[more]

PMID: 30777071

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Project description:Background:Circular RNAs (circRNAs), a novel type of noncoding RNAs, play critical roles in the initiation and progression of cancer. Emerging studies also shows that circRNAs may function as potential markers for cancer diagnosis and treatment. However, the diagnostic value of circRNAs in colorectal cancer (CRC) remains need to be unearthed. Methods:CircRNA microarray was performed to detect the differentially expressed circRNAs in eight plasma samples, including four colorectal cancer (CRC) and four normal samples. Besides, the results of microarray were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, ROC curve evaluation was performed to calculate the diagnostic value of significantly dysregulated circRNAs. In order to predict the potential mechanism of the significant circRNAs, circRNA-miRNA-mRNA network was constructed based on the TargetScan, miRTarBase and MIRDB database, as well as CircInteractome online software. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to further predict the function of meaningful circRNAs. Results:Totally three differentially expressed circRNAs were identified in CRC plasma compared to normal plasma by circRNA microarray analysis, and the results was validated by qRT-PCR. Hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445 were identified and ROC curves analysis was used to calculate the single and joint diagnostic value. Furthermore, GO and KEGG analyses revealed that functions were mainly cancer-related, which indicated that the circRNAs were meaningfully associated with CRC cell proliferation and metastasis. Conclusion:In conclusion, we have identified three circRNAs that are dysregulated in CRC plasma, including hsa_circ_0082182, hsa_circ_0000370 and hsa_circ_0035445. ROC curves showed that these circRNAs might have diagnostic value for colorectal cancer. Furthermore, bioinformatics analysis indicated that the above-mentioned circRNAs might be involved in the development of CRC.

Project description:BACKGROUND: Lung adenocarcinoma is a heterogernous disease that creates challenges for classification and management. The purpose of this study is to identify specific miRNA markers closely associated with the survival of LUAD patients from a large dataset of significantly altered miRNAs, and to assess the prognostic value of this miRNA expression profile for OS in patients with LUAD. METHODS: We obtained miRNA expression profiles and corresponding clinical information for 372 LUAD patients from The Cancer Genome Atlas (TCGA), and identified the most significantly altered miRNAs between tumor and normal samples. Using survival analysis and supervised principal components method, we identified an eight-miRNA signature for the prediction of overall survival (OS) of LUAD patients. The relationship between OS and the identified miRNA signature was self-validated in the TCGA cohort (randomly classified into two subgroups: n?=?186 for the training set and n?=?186 for the testing set). Survival receiver operating characteristic (ROC) analysis was used to assess the performance of survival prediction. The biological relevance of putative miRNA targets was also analyzed using bioinformatics. RESULTS: Sixteen of the 111 most significantly altered miRNAs were associated with OS across different clinical subclasses of the TCGA-derived LUAD cohort. A linear prognostic model of eight miRNAs (miR-31, miR-196b, miR-766, miR-519a-1, miR-375, miR-187, miR-331 and miR-101-1) was constructed and weighted by the importance scores from the supervised principal component method to divide patients into high- and low-risk groups. Patients assigned to the high-risk group exhibited poor OS compared with patients in the low-risk group (hazard ratio [HR]?=?1.99, P <0.001). The eight-miRNA signature is an independent prognostic marker of OS of LUAD patients and demonstrates good performance for predicting 5-year OS (Area Under the respective ROC Curves [AUC]?=?0.626, P?=?0.003), especially for non-smokers (AUC?=?0.686, P?=?0.023). CONCLUSIONS: We identified an eight-miRNA signature that is prognostic of LUAD. The miRNA signature, if validated in other prospective studies, may have important implications in clinical practice, in particular identifying a subgroup of patients with LUAD who are at high risk of mortality.

Dataset Information

A two-circular RNA signature as a noninvasive diagnostic biomarker for lung adenocarcinoma.

Publications

A two-circular RNA signature as a noninvasive diagnostic biomarker for lung adenocarcinoma.

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