A two-circular RNA signature as a noninvasive diagnostic biomarker for lung adenocarcinoma.
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 < 0.0001). In addition, we observed that overexpression of plasma hsa_circ_0086414 was related to EGFR mutations (P = 0.001). Plasma hsa_circ_0005962 displayed significantly different expression before and after surgery in patients with LUAD (P < 0.0001). In vitro experiments suggested that hsa_circ_0005962 promoted LUAD cell proliferation. For future studies, we predicted the circRNA-miRNA-mRNA network for hsa_circ_0005962. Bioinformatics analysis revealed that hsa_circ_0005962 might be involved in LUAD development.


CONCLUSION
A circRNA signature was identified as a potential noninvasive biomarker for LUAD diagnosis.
['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|0000-0002-9538-7601']
D000077192:Adenocarcinoma of Lung D015415:Biomarkers D016022:Case-Control Studies D045744:Cell Line, Tumor D049109:Cell Proliferation D005260:Female D015972:Gene Expression Regulation, Neoplastic D063990:Gene Ontology D053263:Gene Regulatory Networks D006801:Humans D008175:Lung Neoplasms D008297:Male D008875:Middle Aged D000079962:RNA, Circular D012372:ROC Curve D015203:Reproducibility of Results
Biomarker CircRNA LUAD Plasma Hsa_circ_0005962 Hsa_circ_0086414 Diagnosis