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.
Highlights
Lung cancer causes more than 1.6 million deaths per year worldwide, despite current progress in treatment [1]
non-small cell lung carcinoma (NSCLC) patients and normal specimens from a healthy control group were included for meta-analysis
The expression of SETDB1 was significantly increased in NSCLC tissues compared to normal lung tissues (SMD: 0.66; 95% confidence interval (95% CI): 0.52–0.80; p < 0.001) with moderate heterogeneity (I2 = 54.4%; p < 0.001) (Figure 2A)
Summary
Lung cancer causes more than 1.6 million deaths per year worldwide, despite current progress in treatment [1]. The combined use of next-generation high-throughput sequencing (NGS) and ultra-sensitive mass spectrometry technologies has substantially improved our understanding of molecular epigenetic mechanisms, such as histone post-translational modifications (PTMs) and transcriptional regulation in normal and pathological conditions, especially in cancer. Histone PTMs are one of the most important mechanisms of epigenetic regulation of gene expression and chromatin organization. Histone lysine methylation is a key regulatory mechanism of chromatin organization. A large number of studies have substantiated the link between aberrant histone lysine methylation and malignancy, and the roles of KMTs in cancer metastasis [5]. The methylation of histone 3 lysine 9 (H3K9), which is directly involved in heterochromatin formation and both gene repression and silencing [6]. Mutations in KMT genes or abnormal expression of KMTs are found in tumors [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
