Cossiga, Valentina (2022) The intrahepatic dysregulation of thyroid hormone signalling in liver carcinogenesis. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | The intrahepatic dysregulation of thyroid hormone signalling in liver carcinogenesis |
| Autori: | Autore Email Cossiga, Valentina valentina.cossiga@unina.it |
| Data: | 11 Dicembre 2022 |
| Numero di pagine: | 35 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Medicina Clinica e Chirurgia |
| Dottorato: | Terapie avanzate biomediche e chirurgiche |
| Ciclo di dottorato: | 35 |
| Coordinatore del Corso di dottorato: | nome email Pane, Fabrizio [non definito] |
| Tutor: | nome email Morisco, Filomena [non definito] |
| Data: | 11 Dicembre 2022 |
| Numero di pagine: | 35 |
| Parole chiave: | HCC; liver carcinogenesis, thyroid hormone signalling |
| Settori scientifico-disciplinari del MIUR: | Area 06 - Scienze mediche > MED/12 - Gastroenterologia |
| Depositato il: | 06 Mar 2023 07:50 |
| Ultima modifica: | 09 Apr 2025 14:09 |
| URI: | http://www.fedoa.unina.it/id/eprint/14679 |
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: 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.
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