The Prognostic Significance of TRs in Hepatocellular Carcinoma: Insights from TCGA and GEO Databases

Background: Reduced expression of thyroid hormone receptors (TRs) has been observed in various human malignancies, though its predictive value in hepatocellular carcinoma (HCC) remains uncertain. Objective: To explore the predictive value of TRs in patients with hepatocellular carcinoma. Design: The...

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Main Authors: Hao Zhou, Weijie Wang, Ruopeng Liang, Rongtao Zhu, Jiahui Cao, Chenguang Sun, Yuling Sun
Format: Article
Language:English
Published: SAGE Publishing 2025-01-01
Series:Biomarker Insights
Online Access:https://doi.org/10.1177/11772719251315321
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author Hao Zhou
Weijie Wang
Ruopeng Liang
Rongtao Zhu
Jiahui Cao
Chenguang Sun
Yuling Sun
author_facet Hao Zhou
Weijie Wang
Ruopeng Liang
Rongtao Zhu
Jiahui Cao
Chenguang Sun
Yuling Sun
author_sort Hao Zhou
collection DOAJ
description Background: Reduced expression of thyroid hormone receptors (TRs) has been observed in various human malignancies, though its predictive value in hepatocellular carcinoma (HCC) remains uncertain. Objective: To explore the predictive value of TRs in patients with hepatocellular carcinoma. Design: The design was bioinformatic analysis combined with experimental study. Methods: This study utilized Kaplan-Meier analysis of TR expression profiles from The Cancer Genome Atlas (TCGA). Expression levels of TRs in HCC and immune single cells were assessed using datasets from the Gene Expression Omnibus (GEO) and TCGA, analyzed with R software. Cox and logistic regression analyses were also conducted. Functional assays, including wound healing, CCK-8, and Transwell migration assays, were employed to investigate the role of the THRB gene. Results: Kaplan-Meier analysis revealed that low THRB expression was significantly associated with reduced overall survival (OS), 5-year OS and disease-specific survival (DSS) in HCC patients ( P < 0.05), while no significant association was found with THRA expression. Both Cox regression and logistic regression identified low THRB expression as an independent risk factor for HCC. THRB expression was significantly downregulated in tumor tissues compared to non-tumorous tissues in 3 GEO datasets and the TCGA profile. Functional assays confirmed that THRB inhibited HCC cell proliferation and migration. Additionally, single-cell RNA sequencing revealed that THRB was primarily expressed in CD16+ monocytes within tumor tissues and was associated with a poor OS rate. Conclusion: Reduced THRB expression, but not THRA, was correlated with decreased OS in HCC patients.
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spelling doaj-art-c650f7f655cb448abce699330e299c662025-01-25T15:03:19ZengSAGE PublishingBiomarker Insights1177-27192025-01-012010.1177/11772719251315321The Prognostic Significance of TRs in Hepatocellular Carcinoma: Insights from TCGA and GEO DatabasesHao Zhou0Weijie Wang1Ruopeng Liang2Rongtao Zhu3Jiahui Cao4Chenguang Sun5Yuling Sun6Zhengzhou Basic and Clinical Key Laboratory of Hepatopancreatobiliary Diseases, Zhengzhou, ChinaZhengzhou Basic and Clinical Key Laboratory of Hepatopancreatobiliary Diseases, Zhengzhou, ChinaZhengzhou Basic and Clinical Key Laboratory of Hepatopancreatobiliary Diseases, Zhengzhou, ChinaZhengzhou Basic and Clinical Key Laboratory of Hepatopancreatobiliary Diseases, Zhengzhou, ChinaZhengzhou Basic and Clinical Key Laboratory of Hepatopancreatobiliary Diseases, Zhengzhou, ChinaZhengzhou Basic and Clinical Key Laboratory of Hepatopancreatobiliary Diseases, Zhengzhou, ChinaZhengzhou Basic and Clinical Key Laboratory of Hepatopancreatobiliary Diseases, Zhengzhou, ChinaBackground: Reduced expression of thyroid hormone receptors (TRs) has been observed in various human malignancies, though its predictive value in hepatocellular carcinoma (HCC) remains uncertain. Objective: To explore the predictive value of TRs in patients with hepatocellular carcinoma. Design: The design was bioinformatic analysis combined with experimental study. Methods: This study utilized Kaplan-Meier analysis of TR expression profiles from The Cancer Genome Atlas (TCGA). Expression levels of TRs in HCC and immune single cells were assessed using datasets from the Gene Expression Omnibus (GEO) and TCGA, analyzed with R software. Cox and logistic regression analyses were also conducted. Functional assays, including wound healing, CCK-8, and Transwell migration assays, were employed to investigate the role of the THRB gene. Results: Kaplan-Meier analysis revealed that low THRB expression was significantly associated with reduced overall survival (OS), 5-year OS and disease-specific survival (DSS) in HCC patients ( P < 0.05), while no significant association was found with THRA expression. Both Cox regression and logistic regression identified low THRB expression as an independent risk factor for HCC. THRB expression was significantly downregulated in tumor tissues compared to non-tumorous tissues in 3 GEO datasets and the TCGA profile. Functional assays confirmed that THRB inhibited HCC cell proliferation and migration. Additionally, single-cell RNA sequencing revealed that THRB was primarily expressed in CD16+ monocytes within tumor tissues and was associated with a poor OS rate. Conclusion: Reduced THRB expression, but not THRA, was correlated with decreased OS in HCC patients.https://doi.org/10.1177/11772719251315321
spellingShingle Hao Zhou
Weijie Wang
Ruopeng Liang
Rongtao Zhu
Jiahui Cao
Chenguang Sun
Yuling Sun
The Prognostic Significance of TRs in Hepatocellular Carcinoma: Insights from TCGA and GEO Databases
Biomarker Insights
title The Prognostic Significance of TRs in Hepatocellular Carcinoma: Insights from TCGA and GEO Databases
title_full The Prognostic Significance of TRs in Hepatocellular Carcinoma: Insights from TCGA and GEO Databases
title_fullStr The Prognostic Significance of TRs in Hepatocellular Carcinoma: Insights from TCGA and GEO Databases
title_full_unstemmed The Prognostic Significance of TRs in Hepatocellular Carcinoma: Insights from TCGA and GEO Databases
title_short The Prognostic Significance of TRs in Hepatocellular Carcinoma: Insights from TCGA and GEO Databases
title_sort prognostic significance of trs in hepatocellular carcinoma insights from tcga and geo databases
url https://doi.org/10.1177/11772719251315321
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