Identification of risk factors for high-risk dedifferentiation in papillary thyroid carcinoma and construction of discriminative model

ObjectiveWe initially found that the thyroid differentiation score (TDS) was associated with the prognosis of papillary thyroid carcinoma (PTC) patients. Therefore, this study aimed to investigate the influencing factors and construct a discriminative model of high-risk dedifferentiation, and to exp...

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Main Authors: Xiang Liu, Qiao-li Zhu, Zi-yi He, Jing-de Shu, Cheng Xiang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1535966/full
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author Xiang Liu
Qiao-li Zhu
Zi-yi He
Jing-de Shu
Cheng Xiang
author_facet Xiang Liu
Qiao-li Zhu
Zi-yi He
Jing-de Shu
Cheng Xiang
author_sort Xiang Liu
collection DOAJ
description ObjectiveWe initially found that the thyroid differentiation score (TDS) was associated with the prognosis of papillary thyroid carcinoma (PTC) patients. Therefore, this study aimed to investigate the influencing factors and construct a discriminative model of high-risk dedifferentiation, and to explore the possible mechanisms.MethodsData were sourced from the TCGA database. The influences of the TDS, tumor mutation burden, and immune score on the progression-free interval (PFI) were assessed by the Kaplan-Meier method and multivariable Cox regression. Then, logistic regression analyses were utilized to explore the factors of dedifferentiation and a nomogram model was conducted. Additionally, differentially expressed genes (DEGs) were identified using RNA sequencing data, while their regulatory pathways were determined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, the differential expression of key genes of major pathways was explored.ResultsThis study included 391 PTC patients. After analyzing the influences of the three indicators on survival, only TDS showed an association with PFI. Multivariable logistic analysis revealed that the disease duration and PTC subtypes influenced dedifferentiation. The nomogram model based on these two variables showed improved discriminative capability. The study identified 17 overlapping DEGs associated with the dedifferentiation and three primary enrichment pathways, with complement and coagulation cascade pathways being the most significant (P<0.001). The central gene was CD55, which showed high expression in high-risk dedifferentiated and tall cell PTC, and the expression level increased as the disease progressed.ConclusionThis research may contribute to promising identifying high-risk dedifferentiated PTC and also provide a potential therapeutic target.
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spelling doaj-art-b049fa8f3c674a3fbd845d6acd8b9b272025-08-20T03:19:52ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-06-011510.3389/fonc.2025.15359661535966Identification of risk factors for high-risk dedifferentiation in papillary thyroid carcinoma and construction of discriminative modelXiang Liu0Qiao-li Zhu1Zi-yi He2Jing-de Shu3Cheng Xiang4Department of Breast and Thyroid Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaDepartment of Breast and Thyroid Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaDepartment of Breast and Thyroid Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaDepartment of Breast and Thyroid Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, ChinaDepartment of Thyroid Surgery, The Second Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, Zhejiang, ChinaObjectiveWe initially found that the thyroid differentiation score (TDS) was associated with the prognosis of papillary thyroid carcinoma (PTC) patients. Therefore, this study aimed to investigate the influencing factors and construct a discriminative model of high-risk dedifferentiation, and to explore the possible mechanisms.MethodsData were sourced from the TCGA database. The influences of the TDS, tumor mutation burden, and immune score on the progression-free interval (PFI) were assessed by the Kaplan-Meier method and multivariable Cox regression. Then, logistic regression analyses were utilized to explore the factors of dedifferentiation and a nomogram model was conducted. Additionally, differentially expressed genes (DEGs) were identified using RNA sequencing data, while their regulatory pathways were determined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, the differential expression of key genes of major pathways was explored.ResultsThis study included 391 PTC patients. After analyzing the influences of the three indicators on survival, only TDS showed an association with PFI. Multivariable logistic analysis revealed that the disease duration and PTC subtypes influenced dedifferentiation. The nomogram model based on these two variables showed improved discriminative capability. The study identified 17 overlapping DEGs associated with the dedifferentiation and three primary enrichment pathways, with complement and coagulation cascade pathways being the most significant (P<0.001). The central gene was CD55, which showed high expression in high-risk dedifferentiated and tall cell PTC, and the expression level increased as the disease progressed.ConclusionThis research may contribute to promising identifying high-risk dedifferentiated PTC and also provide a potential therapeutic target.https://www.frontiersin.org/articles/10.3389/fonc.2025.1535966/fullthyroid differentiation scorepapillary thyroid carcinomadedifferentiationdifferentially expressed genesCD55
spellingShingle Xiang Liu
Qiao-li Zhu
Zi-yi He
Jing-de Shu
Cheng Xiang
Identification of risk factors for high-risk dedifferentiation in papillary thyroid carcinoma and construction of discriminative model
Frontiers in Oncology
thyroid differentiation score
papillary thyroid carcinoma
dedifferentiation
differentially expressed genes
CD55
title Identification of risk factors for high-risk dedifferentiation in papillary thyroid carcinoma and construction of discriminative model
title_full Identification of risk factors for high-risk dedifferentiation in papillary thyroid carcinoma and construction of discriminative model
title_fullStr Identification of risk factors for high-risk dedifferentiation in papillary thyroid carcinoma and construction of discriminative model
title_full_unstemmed Identification of risk factors for high-risk dedifferentiation in papillary thyroid carcinoma and construction of discriminative model
title_short Identification of risk factors for high-risk dedifferentiation in papillary thyroid carcinoma and construction of discriminative model
title_sort identification of risk factors for high risk dedifferentiation in papillary thyroid carcinoma and construction of discriminative model
topic thyroid differentiation score
papillary thyroid carcinoma
dedifferentiation
differentially expressed genes
CD55
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1535966/full
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