Expression of the major and pro-oncogenic H3K9 lysine methyltransferase SETDB1 in non-small cell lung cancer

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 less than 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. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.

• Fecha de publicación: 2019
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/23638
• Acceso en línea: https://doi.org/10.3390/cancers11081134; https://repository.urosario.edu.co/handle/10336/23638
• Palabra clave: Histone lysine methyltransferase; Messenger rna; Setdb1 protein; Unclassified drug; Article; Controlled study; Disease association; Female; Gene; Human; Human tissue; Lung adenocarcinoma; Major clinical study; Male; Non small cell lung cancer; Pathology; Protein expression; Setdb1 gene; Smoking; Squamous cell lung carcinoma; Transcriptomics; Lysine methyltransferase; Meta-analysis; Non-small cell lung cancer; Setdb1/kmt1e
• License: Abierto (Texto Completo)