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PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer

P21-activated kinases (PAKs) are serine/threonine protein kinases that contribute to several cellular processes. Here, we aimed to determine the prognostic value of PAK1 and its correlation with the clinicopathological characteristics and five-year survival rates in patients with non-small cell lung...

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Autores principales: Chung, Jae Heun, Kim, Taehwa, Kang, Yong Jung, Yoon, Seong Hoon, Kim, Yun Seong, Lee, Sung Kwang, Son, Joo Hyung, Son, Bongsoo, Kim, Do Hyung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729550/
https://www.ncbi.nlm.nih.gov/pubmed/33261184
http://dx.doi.org/10.3390/molecules25235588
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author Chung, Jae Heun
Kim, Taehwa
Kang, Yong Jung
Yoon, Seong Hoon
Kim, Yun Seong
Lee, Sung Kwang
Son, Joo Hyung
Son, Bongsoo
Kim, Do Hyung
author_facet Chung, Jae Heun
Kim, Taehwa
Kang, Yong Jung
Yoon, Seong Hoon
Kim, Yun Seong
Lee, Sung Kwang
Son, Joo Hyung
Son, Bongsoo
Kim, Do Hyung
author_sort Chung, Jae Heun
collection PubMed
description P21-activated kinases (PAKs) are serine/threonine protein kinases that contribute to several cellular processes. Here, we aimed to determine the prognostic value of PAK1 and its correlation with the clinicopathological characteristics and five-year survival rates in patients with non-small cell lung cancer (NSCLC). We evaluated PAK1 mRNA and protein expression in NSCLC cells and resected tumor specimens, as well as in healthy human bronchial epithelial cells and adjacent healthy lung tissues, respectively, for effective comparison. Immunohistochemical tissue microarray analysis of 201 NSCLC specimens showed the correlation of PAK1 expression with clinicopathological characteristics. The mRNA and protein expression of PAK1 were 2.9- and 4.3-fold higher in six of seven NSCLC cell types and human tumors (both, p < 0.001) than in healthy human bronchial epithelial BEAS-2B cells and adjacent healthy lung tissues, respectively. Decreased survival was significantly associated with PAK1 overexpression in the entire cohort (χ(2) = 8.48, p = 0.0036), men (χ(2) = 17.1, p < 0.0001), and current and former smokers (χ(2) = 19.2, p < 0.0001). Notably, epidermal growth factor receptor (EGFR) mutation-positive lung cancer patients with high PAK1 expression showed higher mortality rates than those with low PAK1 expression (91.3% vs. 62.5%, p = 0.02). Therefore, PAK1 overexpression could serve as a molecular target for the treatment of EGFR mutation-positive lung cancer, especially among male patients and current/former smokers.
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spelling pubmed-77295502020-12-12 PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer Chung, Jae Heun Kim, Taehwa Kang, Yong Jung Yoon, Seong Hoon Kim, Yun Seong Lee, Sung Kwang Son, Joo Hyung Son, Bongsoo Kim, Do Hyung Molecules Article P21-activated kinases (PAKs) are serine/threonine protein kinases that contribute to several cellular processes. Here, we aimed to determine the prognostic value of PAK1 and its correlation with the clinicopathological characteristics and five-year survival rates in patients with non-small cell lung cancer (NSCLC). We evaluated PAK1 mRNA and protein expression in NSCLC cells and resected tumor specimens, as well as in healthy human bronchial epithelial cells and adjacent healthy lung tissues, respectively, for effective comparison. Immunohistochemical tissue microarray analysis of 201 NSCLC specimens showed the correlation of PAK1 expression with clinicopathological characteristics. The mRNA and protein expression of PAK1 were 2.9- and 4.3-fold higher in six of seven NSCLC cell types and human tumors (both, p < 0.001) than in healthy human bronchial epithelial BEAS-2B cells and adjacent healthy lung tissues, respectively. Decreased survival was significantly associated with PAK1 overexpression in the entire cohort (χ(2) = 8.48, p = 0.0036), men (χ(2) = 17.1, p < 0.0001), and current and former smokers (χ(2) = 19.2, p < 0.0001). Notably, epidermal growth factor receptor (EGFR) mutation-positive lung cancer patients with high PAK1 expression showed higher mortality rates than those with low PAK1 expression (91.3% vs. 62.5%, p = 0.02). Therefore, PAK1 overexpression could serve as a molecular target for the treatment of EGFR mutation-positive lung cancer, especially among male patients and current/former smokers. MDPI 2020-11-27 /pmc/articles/PMC7729550/ /pubmed/33261184 http://dx.doi.org/10.3390/molecules25235588 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chung, Jae Heun
Kim, Taehwa
Kang, Yong Jung
Yoon, Seong Hoon
Kim, Yun Seong
Lee, Sung Kwang
Son, Joo Hyung
Son, Bongsoo
Kim, Do Hyung
PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer
title PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer
title_full PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer
title_fullStr PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer
title_full_unstemmed PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer
title_short PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer
title_sort pak1 as a potential therapeutic target in male smokers with egfr-mutant non-small cell lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729550/
https://www.ncbi.nlm.nih.gov/pubmed/33261184
http://dx.doi.org/10.3390/molecules25235588
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