Survival-based bioinformatics analysis to identify hub long non-coding RNAs along with lncRNA-miRNA-mRNA network for potential diagnosis/prognosis of thyroid cancer

J Cell Commun Signal. 2022 Sep 23. doi: 10.1007/s12079-022-00697-9. Online ahead of print.

Abstract

Thyroid cancer (TC) is the most common endocrine cancer, accounting for 1.7% of all cancer cases. It has been reported that the existing approach to diagnosing TC is problematic. Therefore, it is essential to develop molecular biomarkers to improve the accuracy of the diagnosis. This study aimed to screen hub lncRNAs in the ceRNA network (ceRNET) connected to TC formation and progression based on the overall survival rate. In this study, first, RNA-seq data from the GDC database were collected. A package called edgeR in R programming language was then used to obtain differentially expressed lncRNAs (DElncRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) in TC patients' samples compared to normal samples. Second, DEmRNAs were analyzed for their functional enrichment. Third, to identify RNAs associated with overall survival, the overall survival of these RNAs was analyzed using the Kaplan-Meier plotter database to create a survival associated with the ceRNA network (survival-related ceRNET). Next, the GeneMANIA plugin was used to construct a PPI network to better understand survival-related DEmRNA interactions. The survival ceRNET was then visualized with the Cytoscape software, and hub genes, including hub lncRNAs and hub mRNAs, were identified using the CytoHubba plugin. We found 45 DElncRNAs, 28 DEmiRNAs, and 723 DEmRNAs among thyroid tumor tissue and non-tumor tissue samples. According to KEGG, GO and DO analyses, 723 DEmRNAs were mainly enriched in cancer-related pathways. Importantly, the results found that ten DElncRNAs, four DEmiRNAs, and 68 DEmRNAs are associated with overall survival. In this account, the PPI network was constructed for 68 survival-related DEmRNAs, and ADAMTS9, DTX4, and CLDN10 were identified as hub genes. The ceRNET was created by combining six lncRNAs, 109 miRNAs, and 22 mRNAs related to survival using Cytoscape. in this network, ten hub RNAs were identified by the CytoHubba plugin, including mRNAs (CTXND1, XKRX, IGFBP2, ENTPD1, GALNT7, ADAMTS9) and lncRNAs (AC090673.1, AL162511.1, LINC02454, AL365259.1). This study suggests that three lncRNAs, including AL162511.1, AC090673.1, and AL365259.1, could be reliable diagnostic biomarkers for TC. The findings of this study provide a basis for future studies on the therapeutic potential of these lncRNAs.

Keywords: Bioinformatics analysis; Hub genes; LncRNA; Thyroid cancer; ceRNA network (ceRNET).