Department of Clinical Laboratory, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, China.
Department of Clinical Laboratory, Ningbo No. 6 Hospital, Ningbo, China.
Front Endocrinol (Lausanne). 2024 Jul 22;15:1397794. doi: 10.3389/fendo.2024.1397794. eCollection 2024.
Thyroid cancer is the most common malignancy of the endocrine system. PANoptosis is a specific form of inflammatory cell death. It mainly includes pyroptosis, apoptosis and necrotic apoptosis. There is increasing evidence that PANoptosis plays a crucial role in tumour development. However, no pathogenic mechanism associated with PANoptosis in thyroid cancer has been identified.
Based on the currently identified PANoptosis genes, a dataset of thyroid cancer patients from the GEO database was analysed. To screen the common differentially expressed genes of thyroid cancer and PANoptosis. To analyse the functional characteristics of PANoptosis-related genes (PRGs) and screen key expression pathways. The prognostic model was established by LASSO regression and key genes were identified. The association between hub genes and immune cells was evaluated based on the CIBERSORT algorithm. Predictive models were validated by validation datasets, immunohistochemistry as well as drug-gene interactions were explored.
The results showed that eight key genes (NUAK2, TNFRSF10B, TNFRSF10C, TNFRSF12A, UNC5B, and PMAIP1) exhibited good diagnostic performance in differentiating between thyroid cancer patients and controls. These key genes were associated with macrophages, CD4+ T cells and neutrophils. In addition, PRGs were mainly enriched in the immunomodulatory pathway and TNF signalling pathway. The predictive performance of the model was confirmed in the validation dataset. The DGIdb database reveals 36 potential therapeutic target drugs for thyroid cancer.
Our study suggests that PANoptosis may be involved in immune dysregulation in thyroid cancer by regulating macrophages, CD4+ T cells and activated T and B cells and TNF signalling pathways. This study suggests potential targets and mechanisms for thyroid cancer development.
甲状腺癌是内分泌系统最常见的恶性肿瘤。PANoptosis 是一种特定形式的炎症细胞死亡。它主要包括细胞焦亡、细胞凋亡和坏死性凋亡。越来越多的证据表明 PANoptosis 在肿瘤发展中起着关键作用。然而，尚未确定与甲状腺癌中 PANoptosis 相关的致病机制。
基于目前已识别的 PANoptosis 基因，对 GEO 数据库中的甲状腺癌患者数据集进行分析。筛选甲状腺癌和 PANoptosis 的常见差异表达基因。分析 PANoptosis 相关基因（PRGs）的功能特征并筛选关键表达途径。通过 LASSO 回归建立预后模型并识别关键基因。基于 CIBERSORT 算法评估关键基因与免疫细胞的关联。通过验证数据集、免疫组织化学和药物-基因相互作用来验证预测模型。
结果表明，八个关键基因（NUAK2、TNFRSF10B、TNFRSF10C、TNFRSF12A、UNC5B 和 PMAIP1）在区分甲状腺癌患者和对照方面表现出良好的诊断性能。这些关键基因与巨噬细胞、CD4+T 细胞和中性粒细胞有关。此外，PRGs 主要富集在免疫调节途径和 TNF 信号通路中。该模型在验证数据集中的预测性能得到了确认。DGIdb 数据库揭示了 36 种潜在的甲状腺癌治疗靶标药物。
我们的研究表明，PANoptosis 可能通过调节巨噬细胞、CD4+T 细胞和活化的 T 和 B 细胞以及 TNF 信号通路，参与甲状腺癌的免疫失调。本研究为甲状腺癌的发生提供了潜在的靶点和机制。
