Construction and Analysis of the Dysregulated ceRNA Network and Identification of Risk Long Noncoding RNAs in Breast Cancer

Xiaojie Su; Zhaoyan Yu; Yuexin Zhang; Jiaxin Chen; Ling Wei; Liang Sun

doi:10.3389/fgene.2021.664393

Construction and Analysis of the Dysregulated ceRNA Network and Identification of Risk Long Noncoding RNAs in Breast Cancer

Front Genet. 2021 Jun 4:12:664393. doi: 10.3389/fgene.2021.664393. eCollection 2021.

Authors

Xiaojie Su¹, Zhaoyan Yu², Yuexin Zhang³, Jiaxin Chen³, Ling Wei³, Liang Sun^{4

5}

Affiliations

¹ College of Medical Laboratory Science and Technology, Harbin Medical University, Daqing, China.
² Department of Otorhinolaryngology, Shandong Provincial Hospital Affiliated to Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
³ School of Medical Informatics, Harbin Medical University, Daqing, China.
⁴ College of Artificial Intelligence and Big Data for Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
⁵ Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China.

Abstract

Breast cancer (BRCA) is the second leading cause of cancer-related mortality in women worldwide. However, the molecular mechanism involved in the development of BRCA is not fully understood. In this study, based on the miRNA-mediated long non-coding RNA (lncRNA)-protein coding gene (PCG) relationship and lncRNA-PCG co-expression information, we constructed and analyzed a specific dysregulated lncRNA-PCG co-expression network in BRCA. Then, we performed the random walk with restart (RWR) method to prioritize BRCA-related lncRNAs through comparing their RWR score and significance. As a result, we identified 30 risk lncRNAs for BRCA, which can distinguish normal and tumor samples. Moreover, through gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, we found that these risk lncRNAs mainly synergistically exerted functions related to cell cycle and DNA separation and replication. At last, we developed a four-lncRNA prognostic signature (including AP000851.1, LINC01977, MAFG-DT, SIAH2-AS1) and assessed the survival accuracy of the signature by performing time-dependent receiver operating characteristic (ROC) analysis. The areas under the ROC curve for 1, 3, 5, and 10 years of survival prediction were 0.68, 0.61, 0.62, and 0.63, respectively. The multivariable Cox regression results verified that the four-lncRNA signature could be used as an independent prognostic biomarker in BRCA. In summary, these results have important reference value for the study of diagnosis, treatment, and prognosis evaluation of BRCA.

Keywords: breast cancer; ceRNA network; competitive endogenous RNA; prognostic signature; random walk with restart; risk lncRNA.