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Open AccessArticle

Expression of the Major and Pro-Oncogenic H3K9 Lysine Methyltransferase SETDB1 in Non-Small Cell Lung Cancer

1
Epigenetics and Cell Fate (EDC), Centre National de la Recherche Scientifique (CNRS), Université de Paris, Université Paris Diderot, F-75013 Paris, France
2
Grupo de investigación Ciencias Básicas Médicas, Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 111221, Colombia
3
School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, Colombia
4
Doctoral Program in Biomedical and Biological Sciences, Universidad del Rosario, Bogotá 111221, Colombia
5
Department of Cardiology, Fundación Cardioinfantil - Instituto de Cardiología, Bogotá 110131, Colombia
6
Department of Hematology-oncology. Fundación Cardioinfantil - Instituto de Cardiología, Bogotá 110131, Colombia
*
Authors to whom correspondence should be addressed.
These authors are equally contributed.
Cancers 2019, 11(8), 1134; https://doi.org/10.3390/cancers11081134
Received: 16 July 2019 / Revised: 5 August 2019 / Accepted: 6 August 2019 / Published: 8 August 2019
(This article belongs to the Special Issue Molecular Profiling of Lung Cancer)
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PDF [2935 KB, uploaded 12 August 2019]
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Abstract

SETDB1 is a key histone lysine methyltransferase involved in gene silencing. The SETDB1 gene is amplified in human lung cancer, where the protein plays a driver role. Here, we investigated the clinical significance of SETDB1 expression in the two major forms of human non-small cell lung carcinoma (NSCLC), i.e., adenocarcinoma (ADC) and squamous cell carcinoma (SCC), by combining a meta-analysis of transcriptomic datasets and a systematic review of the literature. A total of 1140 NSCLC patients and 952 controls were included in the association analyses. Our data revealed higher levels of SETDB1 mRNA in ADC (standardized mean difference, SMD: 0.88; 95% confidence interval, CI: 0.73–1.02; p < 0.001) and SCC (SMD: 0.40; 95% CI: 0.13–0.66; p = 0.003) compared to non-cancerous tissues. For clinicopathological analyses, 2533 ADC and 903 SCC patients were included. Interestingly, SETDB1 mRNA level was increased in NSCLC patients who were current smokers compared to non-smokers (SMD: 0.26; 95% CI: 0.08–0.44; p = 0.004), and when comparing former smokers and non-smokers (p = 0.009). Furthermore, the area under the curve (AUC) given by the summary receiver operator characteristic curve (sROC) was 0.774 (Q = 0.713). Together, our findings suggest a strong foundation for further research to evaluate SETDB1 as a diagnostic biomarker and/or its potential use as a therapeutic target in NSCLC. View Full-Text
Keywords: SETDB1/KMT1E; lysine methyltransferase; non-small cell lung cancer; meta-analysis SETDB1/KMT1E; lysine methyltransferase; non-small cell lung cancer; meta-analysis
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MDPI and ACS Style

Cruz-Tapias, P.; Zakharova, V.; Perez-Fernandez, O.M.; Mantilla, W.; Ramírez-Clavijo, S.; Ait-Si-Ali, S. Expression of the Major and Pro-Oncogenic H3K9 Lysine Methyltransferase SETDB1 in Non-Small Cell Lung Cancer. Cancers 2019, 11, 1134.

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