Abstract
Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer. PTC is typically curable with an excellent survival rate; however, some patients experience disease recurrence or death. This study aimed to discover potential key genes and signaling pathways of PTC, which could provide new insights for thyroid lesions. Four GEO microarray datasets were integrated to screen for candidate genes involved in PTC progression. A total of 164 upregulated and 168 downregulated differentially expressed genes (DEGs) were screened. Gene Ontology/Kyoto Encyclopedia of Genes and Genomes were used in pathway enrichment analyses for DEGs. A protein-protein interaction network was then built and analyzed utilizing STRING and Cytoscape, followed by the identification of 13 hub genes by cytoHubba. CDH3, CTGF, CYR61, OGN, FGF13, and CHRDL1 were selected through survival analyses. Furthermore, immune infiltration, mutations and methylation analysis indicated that these six hub genes played vital roles in immune surveillance and tumor progression. ROC and K-M plots showed that these genes had good prognostic values for PTC which was validated by TCGA dataset. Finally, GSEA for a single hub gene revealed that each candidate hub gene had close associations with PTC development. These findings provided new insights into PTC pathogenesis and identified six candidate gene prognosis signature for PTC.
Highlights
Thyroid cancer (THCA) is one of the most common endocrine malignancies worldwide, and has an increasing incidence (>3% per year) [1]
After filtering out 332 overlapping differentially expressed genes (DEGs), 164 upregulated and 168 downregulated genes were discovered at the intersection of at least three microarray datasets for papillary thyroid cancer (PTC) and peri-tumor for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses
For biological processes (BP), DEGs were mainly enriched in blood coagulation, the bone morphogenetic protein signaling pathway, angiogenesis, wound healing, and extracellular matrix organization (Figure 3A)
Summary
Thyroid cancer (THCA) is one of the most common endocrine malignancies worldwide, and has an increasing incidence (>3% per year) [1]. In 2018, the global incidence of THCA in women was 10.2 per 100,000 (3× that of men), and the disease accounted for 5.1% (1/20 cancer diagnoses) of all cancers in women [2]. Biomarkers in Papillary Thyroid Cancer approximately 37,810 new cases diagnosed and 1,150 deaths in 2019 [1]. Among Chinese women, THCA is the most commonly diagnosed cancer in women before the age of 30, and 67,900 new cases and 4,300 deaths occurred in 2015 [3]. The most common subtype is papillary thyroid cancer (PTC), accounting for about 80% of all THCAs [4]. It is necessary to elucidate the pathogenesis of PTC and identify effective prognostic biomarkers
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