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 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 ( < 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.