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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Main Authors:	Jae Heun Chung, Taehwa Kim, Yong Jung Kang, Seong Hoon Yoon, Yun Seong Kim, Sung Kwang Lee, Joo Hyung Son, Bongsoo Son, Do Hyung Kim
Format:	Article
Language:	English
Published:	MDPI AG 2020-11-01
Series:	Molecules
Subjects:	non-small cell lung cancer p21-activated kinase 1 prognosis male smokers EGFR
Online Access:	https://www.mdpi.com/1420-3049/25/23/5588

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spelling	doaj-01e53ceb18834f1fba7be8148fd5c7672020-11-28T00:07:50ZengMDPI AGMolecules1420-30492020-11-01255588558810.3390/molecules25235588PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung CancerJae Heun Chung0Taehwa Kim1Yong Jung Kang2Seong Hoon Yoon3Yun Seong Kim4Sung Kwang Lee5Joo Hyung Son6Bongsoo Son7Do Hyung Kim8Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, KoreaDepartment of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, KoreaDepartment of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, KoreaDepartment of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, KoreaDepartment of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan 50612, KoreaDepartment of Thoracic and Cardiovascular Surgery, Pusan National University Yangsan Hospital, Yangsan 50612, KoreaDepartment of Thoracic and Cardiovascular Surgery, Pusan National University Yangsan Hospital, Yangsan 50612, KoreaDepartment of Thoracic and Cardiovascular Surgery, Pusan National University Yangsan Hospital, Yangsan 50612, KoreaDepartment of Thoracic and Cardiovascular Surgery, Pusan National University Yangsan Hospital, Yangsan 50612, KoreaP21-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, <i>p</i> < 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<sup>2</sup> = 8.48, <i>p</i> = 0.0036), men (χ<sup>2</sup> = 17.1, <i>p</i> < 0.0001), and current and former smokers (χ<sup>2</sup> = 19.2, <i>p</i> < 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%, <i>p</i> = 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.https://www.mdpi.com/1420-3049/25/23/5588non-small cell lung cancerp21-activated kinase 1prognosismalesmokersEGFR
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Jae Heun Chung Taehwa Kim Yong Jung Kang Seong Hoon Yoon Yun Seong Kim Sung Kwang Lee Joo Hyung Son Bongsoo Son Do Hyung Kim
spellingShingle	Jae Heun Chung Taehwa Kim Yong Jung Kang Seong Hoon Yoon Yun Seong Kim Sung Kwang Lee Joo Hyung Son Bongsoo Son Do Hyung Kim PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer Molecules non-small cell lung cancer p21-activated kinase 1 prognosis male smokers EGFR
author_facet	Jae Heun Chung Taehwa Kim Yong Jung Kang Seong Hoon Yoon Yun Seong Kim Sung Kwang Lee Joo Hyung Son Bongsoo Son Do Hyung Kim
author_sort	Jae Heun Chung
title	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_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_sort	pak1 as a potential therapeutic target in male smokers with egfr-mutant non-small cell lung cancer
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2020-11-01
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, <i>p</i> < 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<sup>2</sup> = 8.48, <i>p</i> = 0.0036), men (χ<sup>2</sup> = 17.1, <i>p</i> < 0.0001), and current and former smokers (χ<sup>2</sup> = 19.2, <i>p</i> < 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%, <i>p</i> = 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.
topic	non-small cell lung cancer p21-activated kinase 1 prognosis male smokers EGFR
url	https://www.mdpi.com/1420-3049/25/23/5588
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PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer

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