A Two-circular RNA Signature As a Noninvasive Diagnostic Biomarker for Lung Adenocarcinoma

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2019 Feb 20

PMID 30777071

Citations 61

Authors

Xiao-Xia Liu

Yi-E Yang

Xiao Liu

Meng-Yu Zhang

Rui Li

Yun-Hong Yin

Yi-Qing Qu

Affiliations

Soon will be listed here.

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 < 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.

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References

Tan S, Gou Q, Pu W, Guo C, Yang Y, Wu K . Circular RNA F-circEA produced from EML4-ALK fusion gene as a novel liquid biopsy biomarker for non-small cell lung cancer. Cell Res. 2018; 28(6):693-695. PMC: 5993747. DOI: 10.1038/s41422-018-0033-7. View

Li S, Teng S, Xu J, Su G, Zhang Y, Zhao J . Microarray is an efficient tool for circRNA profiling. Brief Bioinform. 2018; 20(4):1420-1433. DOI: 10.1093/bib/bby006. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1):7-30. DOI: 10.3322/caac.21442. View

Li X, Yang L, Chen L . The Biogenesis, Functions, and Challenges of Circular RNAs. Mol Cell. 2018; 71(3):428-442. DOI: 10.1016/j.molcel.2018.06.034. View

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. DOI: 10.3322/caac.21492. View

Zhao G, Ding J, Lu C, Lin Z, Guo J . The overexpression of 14-3-3ζ and Hsp27 promotes non–small cell lung cancer progression. Cancer. 2014; 120(5):652-63. DOI: 10.1002/cncr.28452. View

Dudekula D, Panda A, Grammatikakis I, De S, Abdelmohsen K, Gorospe M . CircInteractome: A web tool for exploring circular RNAs and their interacting proteins and microRNAs. RNA Biol. 2015; 13(1):34-42. PMC: 4829301. DOI: 10.1080/15476286.2015.1128065. View

Wu D, Wu T, Chen C, Lee H . PAK1 Is a Novel Therapeutic Target in Tyrosine Kinase Inhibitor-Resistant Lung Adenocarcinoma Activated by the PI3K/AKT Signaling Regardless of EGFR Mutation. Clin Cancer Res. 2016; 22(21):5370-5382. DOI: 10.1158/1078-0432.CCR-15-2724. View

Liu H, Liu Y, Liu W, Zhang W, Xu J . EZH2-mediated loss of miR-622 determines CXCR4 activation in hepatocellular carcinoma. Nat Commun. 2015; 6:8494. PMC: 4598861. DOI: 10.1038/ncomms9494. View

10.

Glazar P, Papavasileiou P, Rajewsky N . circBase: a database for circular RNAs. RNA. 2014; 20(11):1666-70. PMC: 4201819. DOI: 10.1261/rna.043687.113. View

11.

Chen L . The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol. 2016; 17(4):205-11. DOI: 10.1038/nrm.2015.32. View

12.

Qiu M, Xia W, Chen R, Wang S, Xu Y, Ma Z . The Circular RNA circPRKCI Promotes Tumor Growth in Lung Adenocarcinoma. Cancer Res. 2018; 78(11):2839-2851. DOI: 10.1158/0008-5472.CAN-17-2808. View

13.

Li Y, Zheng Q, Bao C, Li S, Guo W, Zhao J . Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res. 2015; 25(8):981-4. PMC: 4528056. DOI: 10.1038/cr.2015.82. View

14.

Koh W, Pan W, Gawad C, Fan H, Kerchner G, Wyss-Coray T . Noninvasive in vivo monitoring of tissue-specific global gene expression in humans. Proc Natl Acad Sci U S A. 2014; 111(20):7361-6. PMC: 4034220. DOI: 10.1073/pnas.1405528111. View

15.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

16.

Viereck J, Thum T . Circulating Noncoding RNAs as Biomarkers of Cardiovascular Disease and Injury. Circ Res. 2017; 120(2):381-399. DOI: 10.1161/CIRCRESAHA.116.308434. View

17.

Hang D, Zhou J, Qin N, Zhou W, Ma H, Jin G . A novel plasma circular RNA circFARSA is a potential biomarker for non-small cell lung cancer. Cancer Med. 2018; 7(6):2783-2791. PMC: 6010816. DOI: 10.1002/cam4.1514. View

18.

Xia S, Feng J, Chen K, Ma Y, Gong J, Cai F . CSCD: a database for cancer-specific circular RNAs. Nucleic Acids Res. 2017; 46(D1):D925-D929. PMC: 5753219. DOI: 10.1093/nar/gkx863. View

19.

Lasda E, Parker R . Circular RNAs Co-Precipitate with Extracellular Vesicles: A Possible Mechanism for circRNA Clearance. PLoS One. 2016; 11(2):e0148407. PMC: 4743949. DOI: 10.1371/journal.pone.0148407. View

20.

Gyorffy B, Surowiak P, Budczies J, Lanczky A . Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung cancer. PLoS One. 2013; 8(12):e82241. PMC: 3867325. DOI: 10.1371/journal.pone.0082241. View