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Identification of signature genes and immune infiltration analysis in thyroid cancer based on PANoptosis related
1Department of Clinical Laboratory, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
PANoptosis, a cell death form, is implicated in thyroid cancer development. This study identifies key genes and pathways involved in immune dysregulation, offering potential therapeutic targets for thyroid cancer.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Thyroid cancer is the most common endocrine malignancy.
- PANoptosis, a cell death form involving pyroptosis, apoptosis, and necrotic apoptosis, is increasingly linked to tumor development.
- The specific role of PANoptosis in thyroid cancer pathogenesis remains unclear.
Purpose of the Study:
- To investigate the role of PANoptosis in thyroid cancer.
- To identify PANoptosis-related genes (PRGs) and their association with thyroid cancer.
- To establish a prognostic model and explore therapeutic targets.
Main Methods:
- Analysis of GEO database thyroid cancer patient data.
- Screening of differentially expressed genes and functional enrichment analysis of PRGs.
- Prognostic model development using LASSO regression and validation through multiple methods.
Main Results:
- Eight key genes (NUAK2, TNFRSF10B, TNFRSF10C, TNFRSF10A, UNC5B, PMAIP1) showed diagnostic value.
- These genes correlate with immune cells like macrophages and CD4+ T cells.
- PRGs are enriched in immunomodulatory and TNF signaling pathways, with 36 potential drug targets identified.
Conclusions:
- PANoptosis may contribute to thyroid cancer via immune dysregulation involving specific immune cells and signaling pathways.
- The identified genes and pathways represent potential therapeutic targets for thyroid cancer treatment.
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