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

• Main Authors: Paola Cruz-Tapias, Vlada Zakharova, Oscar M. Perez-Fernandez, William Mantilla, Sandra Ramírez-Clavijo, Slimane Ait-Si-Ali
• Format: Article
• Language: English
• Published: MDPI AG 2019-08-01
• Series: Cancers
• Subjects: SETDB1/KMT1E; lysine methyltransferase; non-small cell lung cancer; meta-analysis
• Online Access: https://www.mdpi.com/2072-6694/11/8/1134

SETDB1 is a key histone lysine methyltransferase involved in gene silencing. The <i>SETDB1</i> gene is amplified in human lung cancer, where the protein plays a driver role. Here, we investigated the clinical significance of <i>SETDB1</i> 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 <i>SETDB1</i> mRNA in ADC (standardized mean difference, SMD: 0.88; 95% confidence interval, CI: 0.73–1.02; <i>p</i> &lt; 0.001) and SCC (SMD: 0.40; 95% CI: 0.13–0.66; <i>p</i> = 0.003) compared to non-cancerous tissues. For clinicopathological analyses, 2533 ADC and 903 SCC patients were included. Interestingly, <i>SETDB1</i> mRNA level was increased in NSCLC patients who were current smokers compared to non-smokers (SMD: 0.26; 95% CI: 0.08–0.44; <i>p</i> = 0.004), and when comparing former smokers and non-smokers (<i>p</i> = 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.