Decreased expression of thyroid hormone receptor beta (THRB) indicates a poor prognostic factor for liver cancer

Abstract

Abstract Background: The reduced expression of Thyroid hormone receptors (TRs) which are encoded by two genes, THRA and THRB, is found in many human malignancies; however, the clinical prognostic value of TRs in patients with hepatocellular carcinoma (HCC) remains unclear. Methods: The Kaplan-Meier analysis of TRs based on TCGA profile was performed. TRs expression in HCC tumors was evaluated in GEO and TCGA databases by R software. The correlation between the expression of THRB with immune cell infiltration was analyzed on TIMER 2.0 database. Results: Kaplan-Meier analysis demonstrated that low THRB in tumors was significantly associated with worsened overall survival (OS) and disease-specific survival in HCC patients (P < 0.05), not THRA. Subgroup analysis showed that low expression of THRB was associated with reduced 1-year, 3-year, and 5-year OS (all P < 0.05). In addition, the clinical prognostic values of THRB downregulation for OS were more significant in HCC with hepatitis-virus (P = 0.0012), Asian race (P= 0.0038) and male (P = 0.002), and both in with- and without-alcohol-consumption (P = 0.0234 and P = 0.0199, respectively). We found that THRB was significantly down-regulated in tumors compared with nontumor tissues in 3 GEO series (GSE14520, GSE77314, GSE84005) and TCGA profile, but the other 2 GEO series (GSE45436, GSE60502) had no significant down-regulation in tumors. We further calculated the proportion of THRB down-regulated patients with paired samples based on the 4 GEO series and found 56.93% HCC patients with reduced expression of THRB. Immune cell infiltration analysis resulted that neutrophils were the top tumor immune infiltrating cell type associated with THRB. Conclusions: The reduced expression of THRB rather than THRA correlated with worse OS in HCC patients.