Bioinformatics analysis to screen key genes in papillary thyroid carcinoma

Abstract

Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, and its incidence has been on the increase in recent years. However, the molecular mechanism of PTC is unclear and misdiagnosis remains a major issue. Therefore, the present study aimed to investigate this mechanism, and to identify key prognostic biomarkers. Integrated analysis was used to explore differentially expressed genes (DEGs) between PTC and healthy thyroid tissue. To investigate the functions and pathways associated with DEGs, Gene Ontology, pathway and protein-protein interaction (PPI) network analyses were performed. The predictive accuracy of DEGs was evaluated using the receiver operating characteristic (ROC) curve. Based on the four microarray datasets obtained from the Gene Expression Omnibus database, namely GSE33630, GSE27155, GSE3467 and GSE3678, a total of 153 DEGs were identified, including 66 upregulated and 87 downregulated DEGs in PTC compared with controls. These DEGs were significantly enriched in cancer-related pathways and the phosphoinositide 3-kinase-AKT signaling pathway. PPI network analysis screened out key genes, including acetyl-CoA carboxylase beta, cyclin D1, BCL2, and serpin peptidase inhibitor clade A member 1, which may serve important roles in PTC pathogenesis. ROC analysis revealed that these DEGs had excellent predictive performance, thus verifying their potential for clinical diagnosis. Taken together, the findings of the present study suggest that these genes and related pathways are involved in key events of PTC progression and facilitate the identification of prognostic biomarkers.

Impact of the Tumor Microenvironment on the Gene Expression Profile in Papillary Thyroid Cancer

“…The analysis of 500 PTC tumors, based on next-generation sequencing, under the genotyping project Cancer Genome Research Network, confirmed four major molecular events present in the majority of PTC cases: BRAF V600E , RAS, and TERT point mutations as well as RET/PTC rearrangements [4]. Although the PTC transcriptome is well characterized [3,[6][7][8] and correlates with some prognostic and genotypic factors [3,4], biological mechanisms of neoplastic transformation in PTC are not unequivocally elucidated. Nevertheless, these data do not explain the whole biology of PTC tumorigenesis and are only to some extent helpful in diagnostics (BRAF, TERT, RET/PTC rearrangements) [9][10][11][12][13][14] and prognosis (BRAF, TERT) [15][16][17][18].…”

Clinical implications of TPO and AOX1 in pediatric papillary thyroid carcinoma

“…A case-control study reported that a TPO variant is associated with thyroid carcinoma (13). Our previous study and other integrated analyses demonstrated that TPO was significantly downregulated in PTC (10,14). Pathologically, immunohistochemical staining verified that TPO can distinguish PTC from benign thyroid lesions (15).…”

“…However, the etiology and molecular biology of PTC remain clear. Previously, we found that both thyroid peroxidase (TPO) and aldehyde oxidase 1 (AOX1) were downregulated in PTC (10,11). However, further experimental verification and studies of the clinical importance of TPO and AOX1 in PTC must be conducted.…”

ANGPTL1 is a potential biomarker for differentiated thyroid cancer diagnosis and recurrence

“…In TCGA dataset, ‘01’ representeda primary solid tumor, and ‘11’ represented paracancerous tissue. The Gene Expression Omnibus (GEO) datasets GSE3678 ( ) ( 21 ) and GSE3467 ( ) ( 22 ) were also used for ANGPTL1 expression analysis. The data from TCGA dataset were divided into high (n=250) and low (n=251) ANGPTL1 expression groups based on the median values of ANGPTL1 RNA-seq quantification results and further analyzed using GSEA.…”