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.



中文翻译：

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通过生物信息学分析鉴定甲状腺癌中与预后相关的生物标志物

背景：本研究旨在确定与甲状腺癌（TC）预后相关的关键基因，并探索潜在的通路。
方法：使用 GSE66783、GSE58545 和 GSE129562 数据集识别肿瘤和正常组织之间的差异表达基因 (DEG)，然后对 DEG 进行 KEGG 分析。随后构建了DEG的蛋白质-蛋白质相互作用（PPI）网络，以找到整个网络中排名前10位的枢纽基因和种子基因。此外，还探讨了中枢基因的 mRNA 表达和预后价值。关于种子基因，还进行了途径活性评分和GSEA分析。
结果：1）共有183个DEG在三个数据集中一致表达，包括76个上调基因和107个下调基因。DEGs主要富集在p53信号通路、补体和凝血级联反应以及hedgehog信号通路中。2）确定了前10个枢纽基因，包括CCND1、TIMP1、ICAM1、MET、PLAU、LDLR、PLAUR、ITGA2、ITGA3和LGALS3。与正常样品相比，所有中枢基因在 TC 中高度表达。3）CCND1、TIMP1、MET和LGALS3的高表达与患者预后良好有统计学相关性。在 ITGA2 和 ITGA3 高表达的患者中观察到较差的生存率。ICAM1、PLAU 和 PLAUR 表达与患者生存率之间没有关联。LGALS3 和 TIMP1 被进一步确定为 TC 的独立预后因素。4）在10个枢纽基因中，TIMP1被确定为种子基因，表明其在整个网络中的重要性。我们进一步发现，在大多数著名的癌症相关通路中，TIMP1 较高的表达导致较低的通路活性，表明其对 TC 中这些通路的抑制作用。此外，TIMP1 与参与 TC 的 p53 信号通路、补体和凝血级联反应呈正相关。
结论：本研究提供了 7 个与 TC 预后相关的基因，揭示了几个重要的通路，有助于阐明 TC 的发病机制。