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Open AccessArticle

mTOR Expression in Liver Transplant Candidates with Hepatocellular Carcinoma: Impact on Histological Features and Tumour Recurrence

1
Department of Hepatology and Liver Transplantation, CIBERehd, Reina Sofía University Hospital, 14004 Córdoba, Spain
2
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba; 14004 Córdoba, Spain
3
Department of Pathology, Reina Sofía University Hospital, 14004 Córdoba, Spain
4
HPB Surgery and Transplantation, Reina Sofía University Hospital, 14004 Córdoba, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(2), 336; https://doi.org/10.3390/ijms20020336
Received: 6 December 2018 / Revised: 8 January 2019 / Accepted: 9 January 2019 / Published: 15 January 2019
(1) Background: The mammalian target of rapamycin (mTOR) pathway activation is critical for hepatocellular carcinoma (HCC) progression. We aimed to evaluate the mTOR tissue expression in liver transplant (LT) patients and to analyse its influence on post-LT outcomes. (2) Methods: Prospective study including a cohort of HCC patients who underwent LT (2012–2015). MTOR pathway expression was evaluated in the explanted liver by using the “PathScan Intracellular Signalling Array Kit” (Cell Signalling). Kaplan-Meier and Cox regression analyses were performed to evaluate post-LT HCC recurrence. (3) Results: Forty-nine patients were included (average age 56.4 ± 6, 14.3% females). Phospho-mTOR (Ser2448) was over-expressed in peritumoral tissue as compared with tumoral tissue (ΔSignal 22.2%; p < 0.001). The mTOR activators were also increased in peritumoral tissue (phospho-Akt (Thr308) ΔSignal 18.2%, p = 0.004; phospho-AMPKa (Thr172) ΔSignal 56.3%, p < 0.001), as they were the downstream effectors responsible for cell growth/survival (phospho-p70S6K (Thr389) ΔSignal 33.3%, p < 0.001 and phospho-S6RP (Ser235/236) ΔSignal 54.6%, p < 0.001). MTOR expression was increased in patients with multinodular HCC (tumoral p = 0.01; peritumoral p = 0.001). Increased phospho-mTOR in tumoral tissue was associated with higher HCC recurrence rates after LT (23.8% vs. 5.9% at 24 months, p = 0.04). (4) Conclusion: mTOR pathway is over-expressed in patients with multinodular HCC and is it associated with increased post-LT tumour recurrence rates. View Full-Text
Keywords: liver transplantation; hepatocellular carcinoma; mTOR; immunosuppression liver transplantation; hepatocellular carcinoma; mTOR; immunosuppression
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Guerrero, M.; Ferrín, G.; Rodríguez-Perálvarez, M.; González-Rubio, S.; Sánchez-Frías, M.; Amado, V.; Pozo, J.C.; Poyato, A.; Ciria, R.; Ayllón, M.D.; Barrera, P.; Montero, J.L.; de la Mata, M. mTOR Expression in Liver Transplant Candidates with Hepatocellular Carcinoma: Impact on Histological Features and Tumour Recurrence. Int. J. Mol. Sci. 2019, 20, 336.

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