Abstract
The molecular mechanism of the occurrence and development of papillary thyroid carcinoma (PTC) has been widely explored, but has not been completely elucidated. The present study aimed to identify and analyze genes associated with PTC by bioinformatics methods. Two independent datasets were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between PTC tissues and matched non-cancerous tissues were identified using GEO2R tool. The common DEGs in the two datasets were screened out by VennDiagram package, and analyzed by the following tools: KOBAS, Database for Annotation, Visualization, and Integrated Discovery (DAVID), Search tool for the retrieval of interacting genes/proteins (STRING), UALCAN and Gene expression profiling interactive analysis (GEPIA). A total of 513 common DEGs, including 259 common up-regulated and 254 common down-regulated genes in PTC, were screened out. These common up-regulated and down-regulated DEGs were most significantly enriched in cytokine–cytokine receptor interaction and metabolic pathways, respectively. Protein–protein interactions (PPI) network analysis showed that the up-regulated genes: FN1, SDC4, NMU, LPAR5 and the down-regulated genes: BCL2 and CXCL12 were key genes. Survival analysis indicated that the high expression of FN1 and NMU genes significantly decreased disease-free survival of patients with thyroid carcinoma. In conclusion, the genes and pathways identified in the current study will not only contribute to elucidating the pathogenesis of PTC, but also provide prognostic markers and therapeutic targets for PTC.
Highlights
Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid malignancy, and accounts for approximately 75% of all thyroid cancers [1]
We utilized various bioinformatics methods to mine high-throughput gene expression data of PTC and normal thyroid tissues, and identified several key genes associated with PTC, such as Fibronectin 1 (FN1), Syndecan 4 (SDC4), Neuromedin U (NMU), Lysophosphatidic acid receptor 5 (LPAR5), BCL2 apoptosis regulator (BCL2) and C-X-C motif chemokine ligand 12 (CXCL12), which might act as prognostic markers and therapeutic targets for PTC
Other data including 20 paired PTC and noncancerous tissues were from GSE29265, which were generated by the GPL570 platform (Affymetrix Human Genome U133 Plus 2.0 Array) and contributed by Tomas et al
Summary
Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid malignancy, and accounts for approximately 75% of all thyroid cancers [1]. The molecules involved in the occurrence and development of PTC needs to be explored, which will contribute to the finding of prognostic markers and therapeutic targets of PTC. Dong et al [5] found that estrogen could induce the metastatic potential of PTC cells through estrogen receptor α and β. Yin et al [6] found that miR-195 was down-regulated in PTC. Overexpression of miR-195 could significantly inhibit the growth and metastasis of PTC cells by targeting CCND1 and FGF2. Shen et al [7] found that lncRNA PROX1-AS1 could promote the proliferation, invasion and migration of PTC cells and might act as a potential target for PTC therapy. The above findings were obtained based on molecular biological methods, such as Western blot, immunohistochemistry
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