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Cancers (Basel). 2019 Aug 8;11(8). pii: E1134. doi: 10.3390/cancers11081134.

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

Author information

1
Epigenetics and Cell Fate (EDC), Centre National de la Recherche Scientifique (CNRS), Université de Paris, Université Paris Diderot, F-75013 Paris, France. paola.cruz@univ-paris-diderot.fr.
2
Grupo de investigación Ciencias Básicas Médicas, Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 111221, Colombia. paola.cruz@univ-paris-diderot.fr.
3
School of Medicine and Health Sciences, Universidad del Rosario, Bogotá 111221, Colombia. paola.cruz@univ-paris-diderot.fr.
4
Doctoral Program in Biomedical and Biological Sciences, Universidad del Rosario, Bogotá 111221, Colombia. paola.cruz@univ-paris-diderot.fr.
5
Epigenetics and Cell Fate (EDC), Centre National de la Recherche Scientifique (CNRS), Université de Paris, Université Paris Diderot, F-75013 Paris, France.
6
Department of Cardiology, Fundación Cardioinfantil - Instituto de Cardiología, Bogotá 110131, Colombia.
7
Department of Hematology-oncology. Fundación Cardioinfantil - Instituto de Cardiología, Bogotá 110131, Colombia.
8
Grupo de investigación Ciencias Básicas Médicas, Faculty of Natural Sciences and Mathematics, Universidad del Rosario, Bogotá 111221, Colombia.
9
Epigenetics and Cell Fate (EDC), Centre National de la Recherche Scientifique (CNRS), Université de Paris, Université Paris Diderot, F-75013 Paris, France. slimane.aitsiali@univ-paris-diderot.fr.

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.

KEYWORDS:

SETDB1/KMT1E; lysine methyltransferase; meta-analysis; non-small cell lung cancer

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