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Prognostic value of RKIP and p-ERK in gastric cancer

BACKGROUND: The mitogen-activated protein kinase (MAPK) signaling pathway participates in several steps of tumour development and is considered a prominent therapeutic target for the design of chemotherapeutic agents. We evaluated the expressions of extracellular signal-regulated kinase (ERK), mitog...

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Autores principales: Fujimori, Yoshitaka, Inokuchi, Mikito, Takagi, Yoko, Kato, Keiji, Kojima, Kazuyuki, Sugihara, Kenichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351370/
https://www.ncbi.nlm.nih.gov/pubmed/22463874
http://dx.doi.org/10.1186/1756-9966-31-30
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author Fujimori, Yoshitaka
Inokuchi, Mikito
Takagi, Yoko
Kato, Keiji
Kojima, Kazuyuki
Sugihara, Kenichi
author_facet Fujimori, Yoshitaka
Inokuchi, Mikito
Takagi, Yoko
Kato, Keiji
Kojima, Kazuyuki
Sugihara, Kenichi
author_sort Fujimori, Yoshitaka
collection PubMed
description BACKGROUND: The mitogen-activated protein kinase (MAPK) signaling pathway participates in several steps of tumour development and is considered a prominent therapeutic target for the design of chemotherapeutic agents. We evaluated the expressions of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MEK), an upstream regulator of ERK, and Raf kinase inhibitor protein (RKIP), and investigated correlations of these expressions with clinicopathological features and outcomes in gastric cancer. METHODS: Tumour samples were obtained from 105 patients with gastric adenocarcinomas who underwent radical gastrectomy. The expressions of phosphorylated ERK (p-ERK), phosphorylated MEK (p-MEK), and RKIP were analysed by immunohistochemical staining. RESULTS: Expression of RKIP, p-MEK, and p-ERK was found in 69 (66%), 54 (51%), and 64 (61%) of all tumours, respectively. RKIP expression negatively correlated with the depth of invasion (p < 0.001), lymph node involvement (p = 0.028), and Union for International Cancer Control (UICC) stage (p = 0.007). RKIP expression was associated with significantly longer relapse-free survival (RFS) (p = 0.0033), whereas p-MEK was not (p = 0.79). Patients with p-ERK expression had slightly, but not significantly shorter RFS than those without such expression (p = 0.054). Patients with positive p-ERK and negative RKIP expression had significantly shorter RFS than the other patients (p < 0.001). The combination of RKIP and p-ERK expression was an independent prognostic factor (hazard ratio, 2.4; 95% confidence interval, 1.3 - 4.6; p = 0.008). CONCLUSIONS: Our results demonstrated that loss of RKIP was associated with tumour progression and poor survival. Negative RKIP expression combined with positive p-ERK expression was an independent predictor of poor outcomes in patients with gastric cancer.
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spelling pubmed-33513702012-05-15 Prognostic value of RKIP and p-ERK in gastric cancer Fujimori, Yoshitaka Inokuchi, Mikito Takagi, Yoko Kato, Keiji Kojima, Kazuyuki Sugihara, Kenichi J Exp Clin Cancer Res Research BACKGROUND: The mitogen-activated protein kinase (MAPK) signaling pathway participates in several steps of tumour development and is considered a prominent therapeutic target for the design of chemotherapeutic agents. We evaluated the expressions of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MEK), an upstream regulator of ERK, and Raf kinase inhibitor protein (RKIP), and investigated correlations of these expressions with clinicopathological features and outcomes in gastric cancer. METHODS: Tumour samples were obtained from 105 patients with gastric adenocarcinomas who underwent radical gastrectomy. The expressions of phosphorylated ERK (p-ERK), phosphorylated MEK (p-MEK), and RKIP were analysed by immunohistochemical staining. RESULTS: Expression of RKIP, p-MEK, and p-ERK was found in 69 (66%), 54 (51%), and 64 (61%) of all tumours, respectively. RKIP expression negatively correlated with the depth of invasion (p < 0.001), lymph node involvement (p = 0.028), and Union for International Cancer Control (UICC) stage (p = 0.007). RKIP expression was associated with significantly longer relapse-free survival (RFS) (p = 0.0033), whereas p-MEK was not (p = 0.79). Patients with p-ERK expression had slightly, but not significantly shorter RFS than those without such expression (p = 0.054). Patients with positive p-ERK and negative RKIP expression had significantly shorter RFS than the other patients (p < 0.001). The combination of RKIP and p-ERK expression was an independent prognostic factor (hazard ratio, 2.4; 95% confidence interval, 1.3 - 4.6; p = 0.008). CONCLUSIONS: Our results demonstrated that loss of RKIP was associated with tumour progression and poor survival. Negative RKIP expression combined with positive p-ERK expression was an independent predictor of poor outcomes in patients with gastric cancer. BioMed Central 2012-03-31 /pmc/articles/PMC3351370/ /pubmed/22463874 http://dx.doi.org/10.1186/1756-9966-31-30 Text en Copyright ©2012 Fujimori et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Fujimori, Yoshitaka
Inokuchi, Mikito
Takagi, Yoko
Kato, Keiji
Kojima, Kazuyuki
Sugihara, Kenichi
Prognostic value of RKIP and p-ERK in gastric cancer
title Prognostic value of RKIP and p-ERK in gastric cancer
title_full Prognostic value of RKIP and p-ERK in gastric cancer
title_fullStr Prognostic value of RKIP and p-ERK in gastric cancer
title_full_unstemmed Prognostic value of RKIP and p-ERK in gastric cancer
title_short Prognostic value of RKIP and p-ERK in gastric cancer
title_sort prognostic value of rkip and p-erk in gastric cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351370/
https://www.ncbi.nlm.nih.gov/pubmed/22463874
http://dx.doi.org/10.1186/1756-9966-31-30
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