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A novel necroptosis-related gene signature associated with immune landscape for predicting the prognosis of papillary thyroid cancer

Background: Necroptosis, a type of programmed cell death, has been implicated in a variety of cancer-related biological processes. However, the roles of necroptosis-related genes in thyroid cancer yet remain unknown. Methods: A necroptosis-related gene signature was constructed using the least absol...

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Autores principales: Wang, Zhiyuan, Wu, Pu, Shi, Jinyuan, Ji, Xiaoyu, He, Liang, Dong, Wenwu, Wang, Zhihong, Zhang, Hao, Sun, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520455/
https://www.ncbi.nlm.nih.gov/pubmed/36186479
http://dx.doi.org/10.3389/fgene.2022.947216
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author Wang, Zhiyuan
Wu, Pu
Shi, Jinyuan
Ji, Xiaoyu
He, Liang
Dong, Wenwu
Wang, Zhihong
Zhang, Hao
Sun, Wei
author_facet Wang, Zhiyuan
Wu, Pu
Shi, Jinyuan
Ji, Xiaoyu
He, Liang
Dong, Wenwu
Wang, Zhihong
Zhang, Hao
Sun, Wei
author_sort Wang, Zhiyuan
collection PubMed
description Background: Necroptosis, a type of programmed cell death, has been implicated in a variety of cancer-related biological processes. However, the roles of necroptosis-related genes in thyroid cancer yet remain unknown. Methods: A necroptosis-related gene signature was constructed using the least absolute shrinkage and selection operator (LASSO) regression analysis and Cox regression analysis. The predictive value of the prognostic signature was validated in an internal cohort. Additionally, the single-sample gene set enrichment analysis (ssGSEA) was used to examine the relationships between necroptosis and immune cells, immunological functions, and immune checkpoints. Next, the modeled genes expressions were validated in 96 pairs of clinical tumor and normal tissue samples. Finally, the effects of modeled genes on PTC cells were studied by RNA interference approaches in vitro. Results: In this study, the risk signature of seven necroptosis-related genes was created to predict the prognosis of papillary thyroid cancer (PTC) patients, and all patients were divided into high- and low-risk groups. Patients in the high-risk group fared worse in terms of overall survival than those in the low-risk group. The area under the curve (AUC) of the receiving operating characteristic (ROC) curves proved the predictive capability of created signature. The risk score was found to be an independent risk factor for prognosis in multivariate Cox analysis. The low-risk group showed increased immune cell infiltration and immunological activity, implying that they might respond better to immune checkpoint inhibitor medication. Next, GEO database and qRT-PCR in 96 pairs of matched tumorous and non-tumorous tissues were used to validate the expression of the seven modeled genes in PTCs, and the results were compatible with TCGA database. Finally, overexpression of IPMK, KLF9, SPATA2 could significantly inhibit the proliferation, invasion and migration of PTC cells. Conclusion: The created necroptosis associated risk signature has the potential to have prognostic capability in PTC for patient outcome. The findings of this study could pave the way for further research into the link between necroptosis and tumor immunotherapy.
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spelling pubmed-95204552022-09-30 A novel necroptosis-related gene signature associated with immune landscape for predicting the prognosis of papillary thyroid cancer Wang, Zhiyuan Wu, Pu Shi, Jinyuan Ji, Xiaoyu He, Liang Dong, Wenwu Wang, Zhihong Zhang, Hao Sun, Wei Front Genet Genetics Background: Necroptosis, a type of programmed cell death, has been implicated in a variety of cancer-related biological processes. However, the roles of necroptosis-related genes in thyroid cancer yet remain unknown. Methods: A necroptosis-related gene signature was constructed using the least absolute shrinkage and selection operator (LASSO) regression analysis and Cox regression analysis. The predictive value of the prognostic signature was validated in an internal cohort. Additionally, the single-sample gene set enrichment analysis (ssGSEA) was used to examine the relationships between necroptosis and immune cells, immunological functions, and immune checkpoints. Next, the modeled genes expressions were validated in 96 pairs of clinical tumor and normal tissue samples. Finally, the effects of modeled genes on PTC cells were studied by RNA interference approaches in vitro. Results: In this study, the risk signature of seven necroptosis-related genes was created to predict the prognosis of papillary thyroid cancer (PTC) patients, and all patients were divided into high- and low-risk groups. Patients in the high-risk group fared worse in terms of overall survival than those in the low-risk group. The area under the curve (AUC) of the receiving operating characteristic (ROC) curves proved the predictive capability of created signature. The risk score was found to be an independent risk factor for prognosis in multivariate Cox analysis. The low-risk group showed increased immune cell infiltration and immunological activity, implying that they might respond better to immune checkpoint inhibitor medication. Next, GEO database and qRT-PCR in 96 pairs of matched tumorous and non-tumorous tissues were used to validate the expression of the seven modeled genes in PTCs, and the results were compatible with TCGA database. Finally, overexpression of IPMK, KLF9, SPATA2 could significantly inhibit the proliferation, invasion and migration of PTC cells. Conclusion: The created necroptosis associated risk signature has the potential to have prognostic capability in PTC for patient outcome. The findings of this study could pave the way for further research into the link between necroptosis and tumor immunotherapy. Frontiers Media S.A. 2022-09-15 /pmc/articles/PMC9520455/ /pubmed/36186479 http://dx.doi.org/10.3389/fgene.2022.947216 Text en Copyright © 2022 Wang, Wu, Shi, Ji, He, Dong, Wang, Zhang and Sun. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Wang, Zhiyuan
Wu, Pu
Shi, Jinyuan
Ji, Xiaoyu
He, Liang
Dong, Wenwu
Wang, Zhihong
Zhang, Hao
Sun, Wei
A novel necroptosis-related gene signature associated with immune landscape for predicting the prognosis of papillary thyroid cancer
title A novel necroptosis-related gene signature associated with immune landscape for predicting the prognosis of papillary thyroid cancer
title_full A novel necroptosis-related gene signature associated with immune landscape for predicting the prognosis of papillary thyroid cancer
title_fullStr A novel necroptosis-related gene signature associated with immune landscape for predicting the prognosis of papillary thyroid cancer
title_full_unstemmed A novel necroptosis-related gene signature associated with immune landscape for predicting the prognosis of papillary thyroid cancer
title_short A novel necroptosis-related gene signature associated with immune landscape for predicting the prognosis of papillary thyroid cancer
title_sort novel necroptosis-related gene signature associated with immune landscape for predicting the prognosis of papillary thyroid cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520455/
https://www.ncbi.nlm.nih.gov/pubmed/36186479
http://dx.doi.org/10.3389/fgene.2022.947216
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