Comprehensive analysis of lncRNA-mediated ceRNA regulatory networks and key genes associated with papillary thyroid cancer coexistent with Hashimoto’s thyroiditis

Abstract

Objective The incidence of papillary thyroid cancer (PTC) concomitant with Hashimoto’s thyroiditis (HT) is gradually increasing over the past decades. This study aims to identify differentially expressed lncRNAs between tumor tissues of PTC with or without HT and further to confer a better understanding of lncRNA-based competing endogenous RNA (ceRNA) network in PTC with HT. Methods GSE138198 containing tissue mRNA data and GSE192560 containing lncRNA data were utilized to perform differentially expression analysis. The ceRNA network was constructed based on miRNA-mRNA interactions merging with lncRNA-microRNA interactions. Functional enrichment analysis and protein–protein interaction (PPI) analysis were performed. The mRNA levels of core genes in the PPI analysis in tumor tissues collected from 112 PTC patients including 35 cases coexistent with HT were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Results A total of 57 genes and 40 lncRNAs, with value of |log2 fold change (FC)|≥ 1 and the adjusted P-value < 0.05, were deemed as differentially expressed genes and lncRNAs between PTC with and without HT. The pathways most significantly enriched by differentially expressed genes between PTC with and without HT were viral protein interaction with cytokine and cytokine receptor and cytokine-cytokine receptor interaction. CXCL10, CXCL9, CCL5, FCGR3A, and CCR2 owned degree values not less than 10 were deemed as core genes differentially expressed between PTC with and without HT. A total of 76 pairs of lncRNA-miRNA-mRNA ceRNA were obtained. Results of qRT-PCR partially demonstrated the bioinformatics results that the mRNA levels of CXCL10, CXCL9, CCL5, and CCR2 were remarkably elevated in tumor tissues collected from PTC patients coexistent with HT than those without HT (P < 0.001). Conclusion Our study offers a better understanding of the lncRNA-related ceRNA network involved in PTC with HT, providing novel key genes associated with PTC coexistent with HT.

Identification and Preliminary Clinical Validation of Key Extracellular Proteins as the Potential Biomarkers in Hashimoto’s Thyroiditis by Comprehensive Analysis

“…Because the origin and development of HT involve many immune molecules and signaling pathways, it is difficult to completely understand the pathogenesis of HT. CCL5 was found to be remarkably elevated in tumor tissues collected from PTC patients coexistent with HT than those without HT [48], and CXCL9, CXCL10, CXCL11, and CXCL13 were also reportedly upregulated in thyroid tissues from HT patients [26,49]. Our study was consistent with the previous literature reports on the differential expression levels and further revealed the correlation between these chemokines and other immune cells.…”

DARS-AS1: A Vital Oncogenic LncRNA Regulator with Potential for Cancer Prognosis and Therapy

“…These ceRNAs function as defensive shields, safeguarding mRNAs from the inhibitory actions of miRNAs [57]. Within the cancer research, the ceRNA regulatory network orchestrated by lncRNAs plays a pivotal and indispensable role [58][59][60][61][62].…”