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Article

Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations

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Department of Pathology, The Ohio State University, Columbus, OH 43210, USA
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Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA
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Department of Animal Sciences, The Ohio State University, Columbus, OH 43210, USA
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Department of Pharmaceutical Sciences, School of Pharmacy, The University of Montana, Missoula, MT 59812, USA
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2014, 11(9), 9491-9502; https://doi.org/10.3390/ijerph110909491
Received: 27 May 2014 / Revised: 7 August 2014 / Accepted: 25 August 2014 / Published: 12 September 2014
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. View Full-Text
Keywords: lung cancer; non-small cell lung carcinoma; oxidative stress; KRAS; mutation; NQO1; DNA methyl transferase; ERK1/2; c-MET; survivin lung cancer; non-small cell lung carcinoma; oxidative stress; KRAS; mutation; NQO1; DNA methyl transferase; ERK1/2; c-MET; survivin
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MDPI and ACS Style

Yilmaz, A.; Mohamed, N.; Patterson, K.A.; Tang, Y.; Shilo, K.; Villalona-Calero, M.A.; Davis, M.E.; Zhou, X.; Frankel, W.; Otterson, G.A.; Beall, H.D.; Zhao, W. Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations. Int. J. Environ. Res. Public Health 2014, 11, 9491-9502. https://doi.org/10.3390/ijerph110909491

AMA Style

Yilmaz A, Mohamed N, Patterson KA, Tang Y, Shilo K, Villalona-Calero MA, Davis ME, Zhou X, Frankel W, Otterson GA, Beall HD, Zhao W. Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations. International Journal of Environmental Research and Public Health. 2014; 11(9):9491-9502. https://doi.org/10.3390/ijerph110909491

Chicago/Turabian Style

Yilmaz, Ahmet, Nehad Mohamed, Kara A. Patterson, Yan Tang, Konstantin Shilo, Miguel A. Villalona-Calero, Michael E. Davis, Xiaoping Zhou, Wendy Frankel, Gregory A. Otterson, Howard D. Beall, and Weiqiang Zhao. 2014. "Increased NQO1 but Not c-MET and Survivin Expression in Non-Small Cell Lung Carcinoma with KRAS Mutations" International Journal of Environmental Research and Public Health 11, no. 9: 9491-9502. https://doi.org/10.3390/ijerph110909491

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