Identification of Hub lncRNAs Along With lncRNA-miRNA-mRNA Network for Effective Diagnosis and Prognosis of Papillary Thyroid Cancer

Frontiers in Pharmacology

Menglong Li¹  Haiyan Li¹  Yanzhi Guo¹  Xiaoyang Wang¹  Yongmei Xie²  Feng Liu²  Zhihui Li³ 

[1] College of Chemistry, Sichuan University, Chengdu, China;Department of Thyroid Surgery, West China Hospital of Sichuan University, Chengdu, China;Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital of Sichuan University, Chengdu, China;

关键词: papillary thyroid cancer;    hub lncRNAs;    lncRNA-miRNA-mRNA ceRNA network;    diagnosis;    prognosis signature;    bioactive chemicals;   

DOI  :  10.3389/fphar.2021.748867

来源: DOAJ

【 摘 要 】

Long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and progression of different cancers and they have been potential biomarkers for cancer diagnosis and prognosis. As the most common endocrine malignancy, precise diagnosis and prognosis of papillary thyroid cancer (PTC) is of great clinical significance. Here, we aim to identify new hub lncRNAs for marking PTC and constructed prognostics signatures based on lncRNA- miRNA-mRNA competing endogenous RNAs (ceRNA) network to predict overall survival (OS) and disease-free survival (DFS) respectively. Five reliable hub lncRNAs were identified by integrating differential genes of four Gene Expression Omnibus (GEO) gene chips using the RobustRankAggreg (RRA) method. Based on differential analyses and interaction prediction, a lncRNA-mRNA co-expression network and a lncRNA-miRNA-mRNA ceRNA network were established. Then a comprehensive function characterization of the five hub lncRNAs was performed, including validation dataset testing, receiver operating characteristic (ROC) curve analysis, and functional analysis on two networks. All results suggest that these five hub lncRNAs could be potential biomarkers for marking PTC. The ceRNA network was used to identify RNAs which were associated with PTC prognosis. Two prognostic signatures were developed using univariate and step-wise multivariate Cox regression analyses and both of them were independent prognostic indicators for PTC OS and DFS. Tumor microenvironment difference analysis between high and low-risk patients showed that dendritic cells activated and macrophages M0 may be a possible target for immunotherapy of PTC. In addition, disclosing the potential drugs that may reverse the expression of hub genes may improve the prognosis of patients with PTC. Here, connectivity map (CMap) analysis indicates that three bioactive chemicals (pioglitazone, benserazide, and SB-203580) are promising therapeutic agents for PTC. So, the paper presents a comprehensive study on diagnosis, prognosis, and potential drug screening for PTC based on the five hub lncRNAs identified by us.

【 授权许可】

Unknown