The role of thyroid hormone signalling in liver carcinogenesis: A proof of knowledge. (March 2023)

• Record Type: Journal Article
• Authors: Pontillo, G.; Luongo, C.; Giglio, M.C.; Guarino, M.; Rompianesi, G.; Cossiga, V.; De Stefano, M.A.; Montalti, R.; Capasso, M.; Troisi, R.; Salvatore, D.; Morisco, F.
• Is Part Of: Digestive and liver disease. Volume 55(2023)Supplement 1
• Page Start: S20
• Publication Date: 2023-03
• Subjects: Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; 616.33005
• DOI: 10.1016/j.dld.2023.01.036
• Languages: English
• ISSNs: 1590-8658

Abstract

Abstract : Background/Aim: Emerging reports suggest a relationship between thyroid hormones (TH) signalling pathways and liver diseases, including hepatocellular carcinoma (HCC). Although it has been proven that the expression of deiodinases type 1 and 3 (D1-3) changes during induced liver injury, their role is still poorly understood in hepatocarcinogenesis. We aimed to evaluate the role of deiodinases and their regulation in liver carcinogenesis. Methods: This is a proof of knowledge introductory to an ongoing monocentric prospective study. We enrolled 19 patients underwent liver surgery for HCC (10 cases) or for other non-neoplastic liver diseases in non-cirrhotic context (9 controls). We evaluated genes and protein expression of the main TH metabolism factors (D1, Monocarboxylate transporter-MCT8, Thyroid receptors-TR alpha and beta and Kruppel-like factor-KLF-9), with RT-PCR and Western blot analysis in HCC, cirrhotic tissue and healthy liver samples. Results: RT -PCR analysis showed a progressive statistically significant decrease of D1 (p=0.004), MCT-8 (p=0.001) and TRα (p=0.02) mRNA expression from healthy liver to HCC. The expression of KLF9, involved in cell differentiation and proliferation, decreased accordingly (p=0.03). Western Blot analysis showed a decreased expression of D1 protein in all cirrhotic samples (p=0.01), while D3 increased in 50% of HCC (p=0.02). Among HCC patients, D3 expression was associated with more severe liver stiffness (32 kPa, IQR:23.47-35.5, p=0.002) and high BMI (p=0.004). A statistically significant overall survival (OS) difference between D3 positive and D3 negative HCC patients was observed (log rank p=0.003), with a median OS of 17.9 (IQR:15.5-18.7) months for D3 positive vs 41.3 (IQR:35.1-43.8) months in D3 negative. Furthermore, a shorter Progression Free Survival and an increased recurrence rate was observed in D3 positive patients, even if not statistically significant. Conclusions: These preliminary data showed that D3 expression could define a more severe phenotype of HCC and it could be used in clinical practice as negative prognostic biomarker.