PMID- 30650598 OWN - NLM STAT- MEDLINE DCOM- 20190429 LR - 20211204 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 2 DP - 2019 Jan 15 TI - mTOR Expression in Liver Transplant Candidates with Hepatocellular Carcinoma: Impact on Histological Features and Tumour Recurrence. LID - 10.3390/ijms20020336 [doi] LID - 336 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 (DeltaSignal 22.2%; p < 0.001). The mTOR activators were also increased in peritumoral tissue (phospho-Akt (Thr308) DeltaSignal 18.2%, p = 0.004; phospho-AMPKa (Thr172) DeltaSignal 56.3%, p < 0.001), as they were the downstream effectors responsible for cell growth/survival (phospho-p70S6K (Thr389) DeltaSignal 33.3%, p < 0.001 and phospho-S6RP (Ser235/236) DeltaSignal 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. FAU - Guerrero, Marta AU - Guerrero M AD - Department of Hepatology and Liver Transplantation, CIBERehd, Reina Sofia University Hospital, 14004 Cordoba, Spain. martagmisas1987@hotmail.com. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Universidad de Cordoba; 14004 Cordoba, Spain. martagmisas1987@hotmail.com. FAU - Ferrin, Gustavo AU - Ferrin G AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Universidad de Cordoba; 14004 Cordoba, Spain. gusfesa@gmail.com. FAU - Rodriguez-Peralvarez, Manuel AU - Rodriguez-Peralvarez M AUID- ORCID: 0000-0002-1795-2919 AD - Department of Hepatology and Liver Transplantation, CIBERehd, Reina Sofia University Hospital, 14004 Cordoba, Spain. ropeml@hotmail.com. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Universidad de Cordoba; 14004 Cordoba, Spain. ropeml@hotmail.com. FAU - Gonzalez-Rubio, Sandra AU - Gonzalez-Rubio S AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Universidad de Cordoba; 14004 Cordoba, Spain. sayuri254@hotmail.com. FAU - Sanchez-Frias, Marina AU - Sanchez-Frias M AD - Department of Pathology, Reina Sofia University Hospital, 14004 Cordoba, Spain. marinasanchezfrias@gmail.com. FAU - Amado, Victor AU - Amado V AUID- ORCID: 0000-0003-2816-9038 AD - Department of Hepatology and Liver Transplantation, CIBERehd, Reina Sofia University Hospital, 14004 Cordoba, Spain. victoramadotorres@hotmail.com. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Universidad de Cordoba; 14004 Cordoba, Spain. victoramadotorres@hotmail.com. FAU - Pozo, Juan C AU - Pozo JC AUID- ORCID: 0000-0001-7856-9449 AD - Department of Hepatology and Liver Transplantation, CIBERehd, Reina Sofia University Hospital, 14004 Cordoba, Spain. juanc.pozo.sspa@juntadeandalucia.es. FAU - Poyato, Antonio AU - Poyato A AD - Department of Hepatology and Liver Transplantation, CIBERehd, Reina Sofia University Hospital, 14004 Cordoba, Spain. poyato.antonio@gmail.com. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Universidad de Cordoba; 14004 Cordoba, Spain. poyato.antonio@gmail.com. FAU - Ciria, Ruben AU - Ciria R AD - HPB Surgery and Transplantation, Reina Sofia University Hospital, 14004 Cordoba, Spain. rubenciria@gmail.com. FAU - Ayllon, Maria D AU - Ayllon MD AD - HPB Surgery and Transplantation, Reina Sofia University Hospital, 14004 Cordoba, Spain. lolesat83@hotmail.com. FAU - Barrera, Pilar AU - Barrera P AD - Department of Hepatology and Liver Transplantation, CIBERehd, Reina Sofia University Hospital, 14004 Cordoba, Spain. pbarrerabaena@gmail.com. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Universidad de Cordoba; 14004 Cordoba, Spain. pbarrerabaena@gmail.com. FAU - Montero, Jose L AU - Montero JL AD - Department of Hepatology and Liver Transplantation, CIBERehd, Reina Sofia University Hospital, 14004 Cordoba, Spain. jlm14005623@gmail.com. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Universidad de Cordoba; 14004 Cordoba, Spain. jlm14005623@gmail.com. FAU - de la Mata, Manuel AU - de la Mata M AD - Department of Hepatology and Liver Transplantation, CIBERehd, Reina Sofia University Hospital, 14004 Cordoba, Spain. mdelamatagarcia@gmail.com. AD - Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Universidad de Cordoba; 14004 Cordoba, Spain. mdelamatagarcia@gmail.com. LA - eng GR - FIS PI11-02867 and PI14/01469/Instituto de Salud Carlos III/ PT - Journal Article DEP - 20190115 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Carcinoma, Hepatocellular/*genetics/*pathology MH - Female MH - Humans MH - Kaplan-Meier Estimate MH - Liver Neoplasms/*genetics/*pathology MH - *Liver Transplantation MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Neoplasm Recurrence, Local/*pathology MH - Phosphorylation MH - Proportional Hazards Models MH - ROC Curve MH - Signal Transduction MH - TOR Serine-Threonine Kinases/*genetics/metabolism PMC - PMC6359509 OTO - NOTNLM OT - hepatocellular carcinoma OT - immunosuppression OT - liver transplantation OT - mTOR COIS- The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript or in the decision to publish the results. EDAT- 2019/01/18 06:00 MHDA- 2019/04/30 06:00 PMCR- 2019/01/01 CRDT- 2019/01/18 06:00 PHST- 2018/12/06 00:00 [received] PHST- 2019/01/08 00:00 [revised] PHST- 2019/01/09 00:00 [accepted] PHST- 2019/01/18 06:00 [entrez] PHST- 2019/01/18 06:00 [pubmed] PHST- 2019/04/30 06:00 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - ijms20020336 [pii] AID - ijms-20-00336 [pii] AID - 10.3390/ijms20020336 [doi] PST - epublish SO - Int J Mol Sci. 2019 Jan 15;20(2):336. doi: 10.3390/ijms20020336.