Programmed cell death-related gene IL20RA facilitates tumor progression and remodels tumor microenvironment in thyroid cancer

Abstract Programmed cell death (PCD) is a vital biological process that is essential for regulating cell progression and tumor microenvironment. This study aimed to explore the relationship between PCD-related genes expression and prognosis in thyroid cancer (THCA), especially IL20RA, as a potential...

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Main Authors: Yuqi Wang, Yunlong Zhang, Min Liu, Yu Liu, Yu Zeng, Wei Zhang, Shuping Wu, Linfei Hu, Xianhui Ruan, Xiangqian Zheng, Ming Gao, Jingzhu Zhao
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-87059-8
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author Yuqi Wang
Yunlong Zhang
Min Liu
Yu Liu
Yu Zeng
Wei Zhang
Shuping Wu
Linfei Hu
Xianhui Ruan
Xiangqian Zheng
Ming Gao
Jingzhu Zhao
author_facet Yuqi Wang
Yunlong Zhang
Min Liu
Yu Liu
Yu Zeng
Wei Zhang
Shuping Wu
Linfei Hu
Xianhui Ruan
Xiangqian Zheng
Ming Gao
Jingzhu Zhao
author_sort Yuqi Wang
collection DOAJ
description Abstract Programmed cell death (PCD) is a vital biological process that is essential for regulating cell progression and tumor microenvironment. This study aimed to explore the relationship between PCD-related genes expression and prognosis in thyroid cancer (THCA), especially IL20RA, as a potential prognostic marker for THCA. Data from The Cancer Genome Atlas (TCGA) database was utilized to develop a PCD-related risk prediction model based on LASSO regression along with univariate Cox regression. The correlation between PCD-related genes and immune cell infiltration was also assessed. The prognostic value of the key PCD-related gene for THCA was investigated by immunohistochemistry. The immune regulatory function and biological function of the key PCD related molecules were detected by cellular experiments. We identified four PCD-related genes (NPC2, E2F1, IL20RA, and TREM2) and constructed a risk model that exhibited excellent accuracy in predicting the prognosis of THCA. Moreover, we confirmed that high expression of IL20RA related to the poor prognosis of THCA. IL20RA promoted cell proliferation and IL20RA knockdown increased apoptosis and ferroptosis. Analysis of the immune microenvironment and detection of macrophages polarization showed that IL20RA promoted the polarization of M2 macrophages while reducing the polarization of M1. We constructed a prognostic prediction model and identified several PCD-related genes. The function of IL20RA which could potentially provide a foundation for additional investigations into diagnostic markers and treatment targets for THCA.
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spelling doaj-art-7d5080894b10495ca986d7d4900a0aa02025-02-02T12:15:49ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-87059-8Programmed cell death-related gene IL20RA facilitates tumor progression and remodels tumor microenvironment in thyroid cancerYuqi Wang0Yunlong Zhang1Min Liu2Yu Liu3Yu Zeng4Wei Zhang5Shuping Wu6Linfei Hu7Xianhui Ruan8Xiangqian Zheng9Ming Gao10Jingzhu Zhao11Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyDepartment of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyDepartment of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyDepartment of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyDepartment of Thyroid and Breast Surgery, Tianjin Key Laboratory of General Surgery in Construction, Tianjin Union Medical CenterDepartment of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyDepartment of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyDepartment of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyDepartment of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyDepartment of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyDepartment of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyAbstract Programmed cell death (PCD) is a vital biological process that is essential for regulating cell progression and tumor microenvironment. This study aimed to explore the relationship between PCD-related genes expression and prognosis in thyroid cancer (THCA), especially IL20RA, as a potential prognostic marker for THCA. Data from The Cancer Genome Atlas (TCGA) database was utilized to develop a PCD-related risk prediction model based on LASSO regression along with univariate Cox regression. The correlation between PCD-related genes and immune cell infiltration was also assessed. The prognostic value of the key PCD-related gene for THCA was investigated by immunohistochemistry. The immune regulatory function and biological function of the key PCD related molecules were detected by cellular experiments. We identified four PCD-related genes (NPC2, E2F1, IL20RA, and TREM2) and constructed a risk model that exhibited excellent accuracy in predicting the prognosis of THCA. Moreover, we confirmed that high expression of IL20RA related to the poor prognosis of THCA. IL20RA promoted cell proliferation and IL20RA knockdown increased apoptosis and ferroptosis. Analysis of the immune microenvironment and detection of macrophages polarization showed that IL20RA promoted the polarization of M2 macrophages while reducing the polarization of M1. We constructed a prognostic prediction model and identified several PCD-related genes. The function of IL20RA which could potentially provide a foundation for additional investigations into diagnostic markers and treatment targets for THCA.https://doi.org/10.1038/s41598-025-87059-8Programmed cell deathThyroid cancerIL20RAPrognosisTumor microenvironment
spellingShingle Yuqi Wang
Yunlong Zhang
Min Liu
Yu Liu
Yu Zeng
Wei Zhang
Shuping Wu
Linfei Hu
Xianhui Ruan
Xiangqian Zheng
Ming Gao
Jingzhu Zhao
Programmed cell death-related gene IL20RA facilitates tumor progression and remodels tumor microenvironment in thyroid cancer
Scientific Reports
Programmed cell death
Thyroid cancer
IL20RA
Prognosis
Tumor microenvironment
title Programmed cell death-related gene IL20RA facilitates tumor progression and remodels tumor microenvironment in thyroid cancer
title_full Programmed cell death-related gene IL20RA facilitates tumor progression and remodels tumor microenvironment in thyroid cancer
title_fullStr Programmed cell death-related gene IL20RA facilitates tumor progression and remodels tumor microenvironment in thyroid cancer
title_full_unstemmed Programmed cell death-related gene IL20RA facilitates tumor progression and remodels tumor microenvironment in thyroid cancer
title_short Programmed cell death-related gene IL20RA facilitates tumor progression and remodels tumor microenvironment in thyroid cancer
title_sort programmed cell death related gene il20ra facilitates tumor progression and remodels tumor microenvironment in thyroid cancer
topic Programmed cell death
Thyroid cancer
IL20RA
Prognosis
Tumor microenvironment
url https://doi.org/10.1038/s41598-025-87059-8
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