Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives
Abstract Background Pyroptosis, an inflammatory form of programmed cell death, has been implicated in the pathogenesis and progression of several cancers. However, the significance of pyroptosis-related genes (PRGs) in papillary thyroid cancer (PTC) remains unclear. Methods Transcriptome and clinica...
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| Format: | Article |
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BMC
2024-01-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-024-03229-0 |
| _version_ | 1827326136552521728 |
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| author | Fang Li Rui Du Jiedong Kou Jingting Li Le Zhou Daqi Zhang Yantao Fu Gianlorenzo Dionigi Simona Bertoli Hui Sun Nan Liang |
| author_facet | Fang Li Rui Du Jiedong Kou Jingting Li Le Zhou Daqi Zhang Yantao Fu Gianlorenzo Dionigi Simona Bertoli Hui Sun Nan Liang |
| author_sort | Fang Li |
| collection | DOAJ |
| description | Abstract Background Pyroptosis, an inflammatory form of programmed cell death, has been implicated in the pathogenesis and progression of several cancers. However, the significance of pyroptosis-related genes (PRGs) in papillary thyroid cancer (PTC) remains unclear. Methods Transcriptome and clinical data of PTC patients were obtained from The Cancer Genome Atlas. The expression patterns of PRGs were identified by consensus clustering. A prognostic model for predicting the thyroid cancer-free interval (TCFi) employed five machine learning methods. Enrichment and immune-related analyses were performed to elucidate the role of pyroptosis. The responses to radioactive iodine (RAI), immune checkpoint inhibitors (ICIs), molecular targeted therapy (MTT), and chemotherapy (CTx) were predicted based on pyroptosis-derived features. Additionally, the expression of prognostic PRGs was validated via six external datasets, 16 cell lines, and 20 pairs of clinical samples. Results PTC patients were classified into three PyroClusters, C1 exhibited BRFA-like tumors with the highest invasiveness and the worst prognosis, C2 presented RAS-like tumors, and C3 was characterized by gene fusion. Nine PRGs (CXCL8, GJA1, H2BC8, IFI27, PRDM1, PYCARD, SEZ6L2, SIGLEC15, TRAF6) were filtered out to construct a PyroScore prognostic model. A derived nomogram demonstrated superior predictive performance than four clinical staging systems. A strong correlation between pyroptosis and tumor immune microenvironment (TIME) remodeling was observed in mechanistic analyses. Patients with a high PyroScore exhibited “hot” tumor immunophenotypes and had a poorer prognosis but could benefit more from ICIs and CTx (such as paclitaxel). Patients with a low PyroScore were more sensitive to RAI and MTT (such as pazopanib and sorafenib). Conclusions PyroScore model can effectively predict TCFi in patients with PTC. Dysregulated expression of PRGs is associated with the TIME modeling. Pyroptosis features have potential significance for developing novel therapeutic strategies for PTC patients. |
| first_indexed | 2024-03-07T14:40:16Z |
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| id | doaj.art-e9a3f8f256cf49518ae8a87dbf38a777 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-03-07T14:40:16Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
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| series | Cancer Cell International |
| spelling | doaj.art-e9a3f8f256cf49518ae8a87dbf38a7772024-03-05T20:25:29ZengBMCCancer Cell International1475-28672024-01-0124111710.1186/s12935-024-03229-0Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectivesFang Li0Rui Du1Jiedong Kou2Jingting Li3Le Zhou4Daqi Zhang5Yantao Fu6Gianlorenzo Dionigi7Simona Bertoli8Hui Sun9Nan Liang10Division of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid CarcinomaDivision of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid CarcinomaDivision of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid CarcinomaDivision of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid CarcinomaDivision of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid CarcinomaDivision of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid CarcinomaDivision of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid CarcinomaDivision of General Surgery, Endocrine Surgery Unit, Endocrine Surgery Research Institute, Istituto Auxologico Italiano Capitanio (IRCCS), University of MilanDepartment of Food, Environmental and Nutritional Sciences (DeFENS), University of MilanDivision of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid CarcinomaDivision of Thyroid Surgery, The China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Surgical Translational Medicine, Jilin Provincial Precision Medicine Laboratory of Molecular Biology and Translational Medicine on Differentiated Thyroid CarcinomaAbstract Background Pyroptosis, an inflammatory form of programmed cell death, has been implicated in the pathogenesis and progression of several cancers. However, the significance of pyroptosis-related genes (PRGs) in papillary thyroid cancer (PTC) remains unclear. Methods Transcriptome and clinical data of PTC patients were obtained from The Cancer Genome Atlas. The expression patterns of PRGs were identified by consensus clustering. A prognostic model for predicting the thyroid cancer-free interval (TCFi) employed five machine learning methods. Enrichment and immune-related analyses were performed to elucidate the role of pyroptosis. The responses to radioactive iodine (RAI), immune checkpoint inhibitors (ICIs), molecular targeted therapy (MTT), and chemotherapy (CTx) were predicted based on pyroptosis-derived features. Additionally, the expression of prognostic PRGs was validated via six external datasets, 16 cell lines, and 20 pairs of clinical samples. Results PTC patients were classified into three PyroClusters, C1 exhibited BRFA-like tumors with the highest invasiveness and the worst prognosis, C2 presented RAS-like tumors, and C3 was characterized by gene fusion. Nine PRGs (CXCL8, GJA1, H2BC8, IFI27, PRDM1, PYCARD, SEZ6L2, SIGLEC15, TRAF6) were filtered out to construct a PyroScore prognostic model. A derived nomogram demonstrated superior predictive performance than four clinical staging systems. A strong correlation between pyroptosis and tumor immune microenvironment (TIME) remodeling was observed in mechanistic analyses. Patients with a high PyroScore exhibited “hot” tumor immunophenotypes and had a poorer prognosis but could benefit more from ICIs and CTx (such as paclitaxel). Patients with a low PyroScore were more sensitive to RAI and MTT (such as pazopanib and sorafenib). Conclusions PyroScore model can effectively predict TCFi in patients with PTC. Dysregulated expression of PRGs is associated with the TIME modeling. Pyroptosis features have potential significance for developing novel therapeutic strategies for PTC patients.https://doi.org/10.1186/s12935-024-03229-0PyroptosisThyroid cancerTumor immune microenvironmentPrognosisTherapy |
| spellingShingle | Fang Li Rui Du Jiedong Kou Jingting Li Le Zhou Daqi Zhang Yantao Fu Gianlorenzo Dionigi Simona Bertoli Hui Sun Nan Liang Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives Cancer Cell International Pyroptosis Thyroid cancer Tumor immune microenvironment Prognosis Therapy |
| title | Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives |
| title_full | Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives |
| title_fullStr | Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives |
| title_full_unstemmed | Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives |
| title_short | Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives |
| title_sort | elucidating the role of pyroptosis in papillary thyroid cancer prognostic immunological and therapeutic perspectives |
| topic | Pyroptosis Thyroid cancer Tumor immune microenvironment Prognosis Therapy |
| url | https://doi.org/10.1186/s12935-024-03229-0 |
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