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Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer

The Akt (protein kinase B)/mammalian target of rapamycin (mTOR) pathway, which is dysregulated in various cancers, controls the assembly of eukaryotic translation initiation factor 4F (eIF4E) complex. However, whether aberrant expression of phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR) an...

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Autores principales: Lu, Junmi, Zang, Hongjing, Zheng, Hongmei, Zhan, Yuting, Yang, Yang, Zhang, Yuting, Liu, Sile, Feng, Juan, Wen, Qiuyuan, Long, Mengping, Fan, Songqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001968/
https://www.ncbi.nlm.nih.gov/pubmed/32023262
http://dx.doi.org/10.1371/journal.pone.0227768
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author Lu, Junmi
Zang, Hongjing
Zheng, Hongmei
Zhan, Yuting
Yang, Yang
Zhang, Yuting
Liu, Sile
Feng, Juan
Wen, Qiuyuan
Long, Mengping
Fan, Songqing
author_facet Lu, Junmi
Zang, Hongjing
Zheng, Hongmei
Zhan, Yuting
Yang, Yang
Zhang, Yuting
Liu, Sile
Feng, Juan
Wen, Qiuyuan
Long, Mengping
Fan, Songqing
author_sort Lu, Junmi
collection PubMed
description The Akt (protein kinase B)/mammalian target of rapamycin (mTOR) pathway, which is dysregulated in various cancers, controls the assembly of eukaryotic translation initiation factor 4F (eIF4E) complex. However, whether aberrant expression of phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR) and phosphorylated eIF4E (p-eIF4E) is associated with clinicopathological characteristics in surgically resected non-small cell lung cancer (NSCLC) has been rarely reported. Here, we investigated expression of p-Akt, p-mTOR and p-eIF4E proteins in NSCLC by immunohistochemistry and evaluated their correlation with clinicopathological characteristics and prognostic significance. The results showed that the positive percentage of p-Akt, p-mTOR and p-eIF4E was higher in NSCLC. Additionally, p-mTOR and p-eIF4E was dramatically higher in lung adenocarcinoma (both P<0.05). Most importantly, NSCLC patients with lymph node metastasis had significantly elevated expression of p-Akt, p-mTOR and p-eIF4E (all P<0.05). Positive expression of p-Akt, and any positive expression of p-Akt, p-mTOR and p-eIF4E proteins were positively correlated with clinical stages (both P<0.05). Spearman’s rank correlation test revealed that expression of p-Akt was correlated with p-eIF4E and p-mTOR (r = 0.107, P = 0.047; r = 0.287, P<0.001, respectively). Also, p-eIF4E had positive correlation with p-mTOR (r = 0.265, P<0.001). Furthermore, NSCLC patients with increased expression of p-Akt, p-mTOR and p-eIF4E, and any positive expression of above three proteins had lower overall survival rates (all P<0.05). Multivariate Cox regression analysis further indicated thatp-eIF4E was an independent prognostic factor for NSCLC patients (P = 0.046). Taken together, overexpression of p-Akt, p-mTOR and p-eIF4E proteins is associated with metastasis and poor prognosis of NSCLC patients after surgical resection, and positive expression of p-eIF4E protein may act as an independent unfavorable prognostic biomarker for overall survival of NSCLC patients.
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spelling pubmed-70019682020-02-18 Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer Lu, Junmi Zang, Hongjing Zheng, Hongmei Zhan, Yuting Yang, Yang Zhang, Yuting Liu, Sile Feng, Juan Wen, Qiuyuan Long, Mengping Fan, Songqing PLoS One Research Article The Akt (protein kinase B)/mammalian target of rapamycin (mTOR) pathway, which is dysregulated in various cancers, controls the assembly of eukaryotic translation initiation factor 4F (eIF4E) complex. However, whether aberrant expression of phosphorylated Akt (p-Akt), phosphorylated mTOR (p-mTOR) and phosphorylated eIF4E (p-eIF4E) is associated with clinicopathological characteristics in surgically resected non-small cell lung cancer (NSCLC) has been rarely reported. Here, we investigated expression of p-Akt, p-mTOR and p-eIF4E proteins in NSCLC by immunohistochemistry and evaluated their correlation with clinicopathological characteristics and prognostic significance. The results showed that the positive percentage of p-Akt, p-mTOR and p-eIF4E was higher in NSCLC. Additionally, p-mTOR and p-eIF4E was dramatically higher in lung adenocarcinoma (both P<0.05). Most importantly, NSCLC patients with lymph node metastasis had significantly elevated expression of p-Akt, p-mTOR and p-eIF4E (all P<0.05). Positive expression of p-Akt, and any positive expression of p-Akt, p-mTOR and p-eIF4E proteins were positively correlated with clinical stages (both P<0.05). Spearman’s rank correlation test revealed that expression of p-Akt was correlated with p-eIF4E and p-mTOR (r = 0.107, P = 0.047; r = 0.287, P<0.001, respectively). Also, p-eIF4E had positive correlation with p-mTOR (r = 0.265, P<0.001). Furthermore, NSCLC patients with increased expression of p-Akt, p-mTOR and p-eIF4E, and any positive expression of above three proteins had lower overall survival rates (all P<0.05). Multivariate Cox regression analysis further indicated thatp-eIF4E was an independent prognostic factor for NSCLC patients (P = 0.046). Taken together, overexpression of p-Akt, p-mTOR and p-eIF4E proteins is associated with metastasis and poor prognosis of NSCLC patients after surgical resection, and positive expression of p-eIF4E protein may act as an independent unfavorable prognostic biomarker for overall survival of NSCLC patients. Public Library of Science 2020-02-05 /pmc/articles/PMC7001968/ /pubmed/32023262 http://dx.doi.org/10.1371/journal.pone.0227768 Text en © 2020 Lu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lu, Junmi
Zang, Hongjing
Zheng, Hongmei
Zhan, Yuting
Yang, Yang
Zhang, Yuting
Liu, Sile
Feng, Juan
Wen, Qiuyuan
Long, Mengping
Fan, Songqing
Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer
title Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer
title_full Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer
title_fullStr Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer
title_full_unstemmed Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer
title_short Overexpression of p-Akt, p-mTOR and p-eIF4E proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer
title_sort overexpression of p-akt, p-mtor and p-eif4e proteins associates with metastasis and unfavorable prognosis in non-small cell lung cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7001968/
https://www.ncbi.nlm.nih.gov/pubmed/32023262
http://dx.doi.org/10.1371/journal.pone.0227768
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