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Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations
Cigarette smoking is one of the most significant public health issues and the most common environmental cause of preventable cancer deaths worldwide. EGFR (Epidermal Growth Factor Receptor)-targeted therapy has been used in the treatment of LC (lung cancer), mainly caused by the carcinogens in cigar...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199031/ https://www.ncbi.nlm.nih.gov/pubmed/25222473 http://dx.doi.org/10.3390/ijerph110909491 |
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author | Yilmaz, Ahmet Mohamed, Nehad Patterson, Kara A. Tang, Yan Shilo, Konstantin Villalona-Calero, Miguel A. Davis, Michael E. Zhou, Xiaoping Frankel, Wendy Otterson, Gregory A. Beall, Howard D. Zhao, Weiqiang |
author_facet | Yilmaz, Ahmet Mohamed, Nehad Patterson, Kara A. Tang, Yan Shilo, Konstantin Villalona-Calero, Miguel A. Davis, Michael E. Zhou, Xiaoping Frankel, Wendy Otterson, Gregory A. Beall, Howard D. Zhao, Weiqiang |
author_sort | Yilmaz, Ahmet |
collection | PubMed |
description | Cigarette smoking is one of the most significant public health issues and the most common environmental cause of preventable cancer deaths worldwide. EGFR (Epidermal Growth Factor Receptor)-targeted therapy has been used in the treatment of LC (lung cancer), mainly caused by the carcinogens in cigarette smoke, with variable success. Presence of mutations in the KRAS (Kirsten rat sarcoma viral oncogene homolog) driver oncogene may confer worse prognosis and resistance to treatment for reasons not fully understood. NQO1 (NAD(P)H:quinone oxidoreductase), also known as DT-diaphorase, is a major regulator of oxidative stress and activator of mitomycins, compounds that have been targeted in over 600 pre-clinical trials for treatment of LC. We sequenced KRAS and investigated expression of NQO1 and five clinically relevant proteins (DNMT1, DNMT3a, ERK1/2, c-MET, and survivin) in 108 patients with non-small cell lung carcinoma (NSCLC). NQO1, ERK1/2, DNMT1, and DNMT3a but not c-MET and survivin expression was significantly more frequent in patients with KRAS mutations than those without, suggesting the following: (1) oxidative stress may play an important role in the pathogenesis, worse prognosis, and resistance to treatment reported in NSCLC patients with KRAS mutations, (2) selecting patients based on their KRAS mutational status for future clinical trials may increase success rate, and (3) since oxidation of nucleotides also specifically induces transversion mutations, the high rate of KRAS transversions in lung cancer patients may partly be due to the increased oxidative stress in addition to the known carcinogens in cigarette smoke. |
format | Online Article Text |
id | pubmed-4199031 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-41990312014-10-17 Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations Yilmaz, Ahmet Mohamed, Nehad Patterson, Kara A. Tang, Yan Shilo, Konstantin Villalona-Calero, Miguel A. Davis, Michael E. Zhou, Xiaoping Frankel, Wendy Otterson, Gregory A. Beall, Howard D. Zhao, Weiqiang Int J Environ Res Public Health Article Cigarette smoking is one of the most significant public health issues and the most common environmental cause of preventable cancer deaths worldwide. EGFR (Epidermal Growth Factor Receptor)-targeted therapy has been used in the treatment of LC (lung cancer), mainly caused by the carcinogens in cigarette smoke, with variable success. Presence of mutations in the KRAS (Kirsten rat sarcoma viral oncogene homolog) driver oncogene may confer worse prognosis and resistance to treatment for reasons not fully understood. NQO1 (NAD(P)H:quinone oxidoreductase), also known as DT-diaphorase, is a major regulator of oxidative stress and activator of mitomycins, compounds that have been targeted in over 600 pre-clinical trials for treatment of LC. We sequenced KRAS and investigated expression of NQO1 and five clinically relevant proteins (DNMT1, DNMT3a, ERK1/2, c-MET, and survivin) in 108 patients with non-small cell lung carcinoma (NSCLC). NQO1, ERK1/2, DNMT1, and DNMT3a but not c-MET and survivin expression was significantly more frequent in patients with KRAS mutations than those without, suggesting the following: (1) oxidative stress may play an important role in the pathogenesis, worse prognosis, and resistance to treatment reported in NSCLC patients with KRAS mutations, (2) selecting patients based on their KRAS mutational status for future clinical trials may increase success rate, and (3) since oxidation of nucleotides also specifically induces transversion mutations, the high rate of KRAS transversions in lung cancer patients may partly be due to the increased oxidative stress in addition to the known carcinogens in cigarette smoke. MDPI 2014-09-12 2014-09 /pmc/articles/PMC4199031/ /pubmed/25222473 http://dx.doi.org/10.3390/ijerph110909491 Text en © 2014 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 license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Yilmaz, Ahmet Mohamed, Nehad Patterson, Kara A. Tang, Yan Shilo, Konstantin Villalona-Calero, Miguel A. Davis, Michael E. Zhou, Xiaoping Frankel, Wendy Otterson, Gregory A. Beall, Howard D. Zhao, Weiqiang Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations |
title | Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations |
title_full | Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations |
title_fullStr | Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations |
title_full_unstemmed | Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations |
title_short | Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations |
title_sort | increased nqo1 but not c-met and survivin expression in non-small cell lung carcinoma with kras mutations |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4199031/ https://www.ncbi.nlm.nih.gov/pubmed/25222473 http://dx.doi.org/10.3390/ijerph110909491 |
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