The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance

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datacite.alternateIdentifier.citationVIRCHOWS ARCHIV,Vol.465,25-33,2014
datacite.alternateIdentifier.doi10.1007/s00428-014-1588-4
datacite.creatorTapia, Oscar
datacite.creatorRiquelme, Ismael
datacite.creatorLeal, Pamela
datacite.creatorSandoval, Alejandra
datacite.creatorAedo, Susana
datacite.creatorWeber, Helga
datacite.creatorLetelier, Pablo
datacite.creatorBellolio, Enrique
datacite.creatorVillaseca, Miguel
datacite.creatorGarcia, Patricia
datacite.creatorCarlos Roa, Juan
datacite.date2014
datacite.subject.englishAKT
datacite.subject.englishmTOR
datacite.subject.englishImmunohistochemistry
datacite.subject.englishGastric cancer
datacite.titleThe PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance
dc.date.accessioned2021-04-30T16:47:48Z
dc.date.available2021-04-30T16:47:48Z
dc.description.abstractSignaling pathway alterations are important in the development of gastric cancer (GC). Deregulation of the PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism, and angiogenesis. Our goal was to assess expression of proteins involved in the PI3K/AKT/mTOR pathway by immunohistochemistry (IHC) in tumor and nontumor gastric mucosa from patients with advanced GC. We evaluated 71 tumor and 71 nontumor gastric mucosa samples from advanced GC patients, selected from Hernan Henriquez Aravena Hospital (Temuco, Chile). The targets studied were PI3K, AKT, p-AKT, PTEN, mTOR, p-mTOR, P70S6K1, p-P70S6K1, 4E-BP1, p-4E-BP1, eIF4E, and p-eIF4E. Expression data were correlated with clinicomorphological data. Descriptive and analytical statistics were used (95 % confidence interval, p < 0.05). For survival analyses, the Kaplan-Meier method and the log-rank test were used. PI3K, AKT, p-AKT, p-mTOR, p-4E-BP1, P70S6K1, p-P70S6K1, eIF-4E, and p-eIF-4E proteins were significantly overexpressed in tumor tissue. Conversely, PTEN was underexpressed in tumor tissue, notably in pT3-pT4 tumors (p = 0.02) and tumors with lymph node metastases (p < 0.001). P70S6K1 expression was associated with pT3-pT4 tumors (p = 0.03). Moreover, PI3K (p = 0.004), AKT (p = 0.01), p-AKT (p = 0.01), P70S6K1 (p = 0.04), p-P70S6K1 (p = 0.001), and eIF-4E (p = 0.004) were overexpressed in tumors with lymph node metastases. Low expression of 4E-BP1 was associated with poor overall survival (p = 0.03). Our results suggest that the PI3K/AKT/mTOR pathway is activated in GC, with overexpression in tumor tissue of most of the studied proteins (total and phosphorylated). These might be considered as target for specific targeted therapy in GC.
dc.identifier.urihttp://repositoriodigital.uct.cl/handle/10925/3536
dc.language.isoen
dc.publisherSPRINGER
dc.sourceVIRCHOWS ARCHIV
oaire.resourceTypeArticle
uct.catalogadorWOS
uct.indizacionSCI
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