Background: This study aimed to identify the key genes associated with prognosis in thyroid cancer (TC), and to explore potential pathways.
Methods: GSE66783, GSE58545, and GSE129562 datasets were used to identify differentially expressed genes (DEGs) between tumor and normal tissues, followed by KEGG analyses on DEGs. The protein–protein interaction (PPI) network of DEGs was subsequently constructed to find the top 10 hub genes and seed genes in the whole network. Furthermore, the mRNA expressions of hub genes and prognostic values were explored. Regarding the seed gene, pathway activity score and GSEA analyses were conducted as well.
Results: 1) A total of 183 DEGs were consistently expressed in three datasets comprising 76 up-regulated and 107 down-regulated genes. DEGs were mainly enriched in the p53 signaling pathway, complement and coagulation cascades, and hedgehog signaling pathway. 2) The top 10 hub genes, including CCND1, TIMP1, ICAM1, MET, PLAU, LDLR, PLAUR, ITGA2, ITGA3, and LGALS3, were identified. All hub genes were highly expressed in TC compared with normal samples. 3) High expression of CCND1, TIMP1, MET, and LGALS3 statistically correlated with a favorable prognosis of patients. Poor survival was observed in patients with ITGA2 and ITGA3 high expression. There was no association between ICAM1, PLAU, and PLAUR expression and survival of patients. LGALS3 and TIMP1 were further identified as independent prognostic factors in TC. 4) Among 10 hub genes, TIMP1 was determined as the seed gene, indicating its significance in the whole network. We further found that in most of the famous cancer-related pathways, TIMP1 higher expression caused a lower pathway activity, suggesting its inhibitory effect to these pathways in TC. In addition, TIMP1 positively correlated with the p53 signaling pathway, complement, and coagulation cascades involved in TC.
Conclusion: The present study provided seven prognosis-associated genes in TC and revealed several significant pathways, which contributed to elucidate the pathogenesis of TC.
Keywords: thyroid cancer, differentially expressed genes, prognosis, TIMP1