RT Journal Article
T1 mTOR Expression in Liver Transplant Candidates with Hepatocellular Carcinoma: Impact on Histological Features and Tumour Recurrence.
A1 Guerrero, Marta
A1 Ferrin, Gustavo
A1 Rodriguez-Peralvarez, Manuel
A1 Gonzalez-Rubio, Sandra
A1 Sanchez-Frias, Marina
A1 Amado, Viíctor
A1 Pozo, Juan C
A1 Poyato, Antonio
A1 Ciria, Ruben
A1 Ayllon, Maria D
A1 Barrera, Pilar
A1 Montero, Jose L
A1 de la Mata, Manuel
K1 Hepatocellular carcinoma
K1 Immunosuppression
K1 Liver transplantation
K1 mTOR
AB (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) ∆Signal 18.2%, p = 0.004; phospho-AMPKa (Thr172) ∆Signal 56.3%, p < 0.001), as they were the downstream effectors responsible for cell growth/survival (phospho-p70S6K (Thr389) ∆Signal 33.3%, p < 0.001 and phospho-S6RP (Ser235/236) ∆Signal 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.
PB MDPI
YR 2019
FD 2019-01-09
LK http://hdl.handle.net/10668/13429
UL http://hdl.handle.net/10668/13429
LA en
NO Guerrero M, Ferrín G, Rodríguez-Perálvarez M, González-Rubio S, Sánchez-Frías M, Amado V, et al. mTOR Expression in Liver Transplant Candidates with Hepatocellular Carcinoma: Impact on Histological Features and Tumour Recurrence. Int J Mol Sci. 2019 Jan 15;20(2):336
DS RISalud
RD Apr 11, 2025