PDF(Pubmed)
Abstract：
BACKGROUND: Recurrent and metastatic thyroid cancer is more invasive and can transform to dedifferentiated thyroid cancer, thus leading to a severe decline in the 10-year survival. The thyroid-stimulating hormone receptor (TSHR) plays an important role in differentiation process. We aim to find a therapeutic target in redifferentiation strategies for thyroid cancer.
METHODS: Our study integrated the differentially expressed genes acquired from the Gene Expression Omnibus database by comparing TSHR expression levels in the Cancer Genome Atlas database. We conducted functional enrichment analysis and verified the expression of these genes by RT-PCR in 68 pairs of thyroid tumor and paratumor tissues. Artificial intelligence-enabled virtual screening was combined with the VirtualFlow platform for deep docking.
RESULTS: We identified five genes (KCNJ16, SLC26A4, TG, TPO, and SYT1) as potential cancer treatment targets. TSHR and KCNJ16 were downregulated in the thyroid tumor tissues, compared with paired normal tissues. In addition, KCNJ16 was lower in the vascular/capsular invasion group. Enrichment analyses revealed that KCNJ16 may play a significant role in cell growth and differentiation. The inward rectifier potassium channel 5.1 (Kir5.1, encoded by KCNJ16) emerged as an interesting target in thyroid cancer. Artificial intelligence-facilitated molecular docking identified Z2087256678_2, Z2211139111_1, Z2211139111_2, and PV-000592319198_1 (-7.3 kcal/mol) as the most potent commercially available molecular targeting Kir5.1.
CONCLUSIONS: This study may provide greater insights into the differentiation features associated with TSHR expression in thyroid cancer, and Kir5.1 may be a potential therapeutic target in the redifferentiation strategies for recurrent and metastatic thyroid cancer.
METHODS: Our study integrated the differentially expressed genes acquired from the Gene Expression Omnibus database by comparing TSHR expression levels in the Cancer Genome Atlas database. We conducted functional enrichment analysis and verified the expression of these genes by RT-PCR in 68 pairs of thyroid tumor and paratumor tissues. Artificial intelligence-enabled virtual screening was combined with the VirtualFlow platform for deep docking.
RESULTS: We identified five genes (KCNJ16, SLC26A4, TG, TPO, and SYT1) as potential cancer treatment targets. TSHR and KCNJ16 were downregulated in the thyroid tumor tissues, compared with paired normal tissues. In addition, KCNJ16 was lower in the vascular/capsular invasion group. Enrichment analyses revealed that KCNJ16 may play a significant role in cell growth and differentiation. The inward rectifier potassium channel 5.1 (Kir5.1, encoded by KCNJ16) emerged as an interesting target in thyroid cancer. Artificial intelligence-facilitated molecular docking identified Z2087256678_2, Z2211139111_1, Z2211139111_2, and PV-000592319198_1 (-7.3 kcal/mol) as the most potent commercially available molecular targeting Kir5.1.
CONCLUSIONS: This study may provide greater insights into the differentiation features associated with TSHR expression in thyroid cancer, and Kir5.1 may be a potential therapeutic target in the redifferentiation strategies for recurrent and metastatic thyroid cancer.
摘要：
背景：复发和转移性甲状腺癌更具侵袭性，可以转变为去分化甲状腺癌，从而导致10年生存率严重下降。促甲状腺激素受体(TSHR)在分化过程中起重要作用。我们的目标是在甲状腺癌的再分化策略中找到治疗靶标。
方法：我们的研究通过比较癌症基因组图谱数据库中的TSHR表达水平，整合了从基因表达综合数据库中获得的差异表达基因。我们进行了功能富集分析，并通过RT-PCR验证了这些基因在68对甲状腺肿瘤和瘤旁组织中的表达。支持人工智能的虚拟筛选与VirtualFlow平台相结合，实现深度对接。
结果：我们确定了五个基因（KCNJ16，SLC26A4，TG，TPO,和SYT1）作为潜在的癌症治疗靶标。TSHR和KCNJ16在甲状腺肿瘤组织中表达下调,与配对的正常组织相比。此外,KCNJ16在血管/包膜侵犯组中较低。富集分析显示KCNJ16可能在细胞生长和分化中起重要作用。内向整流钾通道5.1（Kir5.1，由KCNJ16编码）成为甲状腺癌的一个有趣的靶标。人工智能促进的分子对接确定Z2087256678_2，Z2211139111_1，Z2211139111_2和PV-000592319198_1（-7.3kcal/mol）是最有效的市售分子靶向Kir5.1。
结论：这项研究可能为甲状腺癌中与TSHR表达相关的分化特征提供更深入的见解，Kir5.1可能是复发和转移性甲状腺癌再分化策略的潜在治疗靶点。
方法：我们的研究通过比较癌症基因组图谱数据库中的TSHR表达水平，整合了从基因表达综合数据库中获得的差异表达基因。我们进行了功能富集分析，并通过RT-PCR验证了这些基因在68对甲状腺肿瘤和瘤旁组织中的表达。支持人工智能的虚拟筛选与VirtualFlow平台相结合，实现深度对接。
结果：我们确定了五个基因（KCNJ16，SLC26A4，TG，TPO,和SYT1）作为潜在的癌症治疗靶标。TSHR和KCNJ16在甲状腺肿瘤组织中表达下调,与配对的正常组织相比。此外,KCNJ16在血管/包膜侵犯组中较低。富集分析显示KCNJ16可能在细胞生长和分化中起重要作用。内向整流钾通道5.1（Kir5.1，由KCNJ16编码）成为甲状腺癌的一个有趣的靶标。人工智能促进的分子对接确定Z2087256678_2，Z2211139111_1，Z2211139111_2和PV-000592319198_1（-7.3kcal/mol）是最有效的市售分子靶向Kir5.1。
结论：这项研究可能为甲状腺癌中与TSHR表达相关的分化特征提供更深入的见解，Kir5.1可能是复发和转移性甲状腺癌再分化策略的潜在治疗靶点。
