RARβ Promoter Methylation as an Epigenetic Mechanism of Gene Silencing in Non-small Cell Lung Cancer
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The retinoid acid receptor-β (RARβ) gene is one of the tumor suppressor genes (TSGs), which is frequently deleted or epigenetically silenced at an early stage of tumor progression. In this study we investigated the promoter methylation and expression status of the RARß gene in 60 surgically resected non-small cell lung cancer (NSCLC) tissue samples and 60 corresponding unchanged lung tissue samples, using methylation-specific PCR and real-time-polymerase chain reaction (qPCR) techniques. We correlated the results with the pathological features of tumors and clinical characteristics of patients. qPCR analysis detected a significantly lower RARß expression in the patients with adenocarcinoma (AC) and large cell carcinoma (LCC) than in those with squamous cell carcinoma (SCC) (AC vs. SCC, p = 0.032; AC and LCC vs. SCC, p = 0.013). Additionally, significantly lower expression of the RARß gene was revealed in the patients with non-squamous cell cancer with a history of smoking assessed as pack-years (PY <40 vs. PY ≥40, p = 0.045). Regarding RARß promoter methylation, we found significant differences in the methylation index in the SCC group when considering pTNM staging; with higher index values in T1a + T1b compared with T2a + T2b and T3 + T4 groups (p = 0.024). There was no correlation between the methylation status and expression level of the RARß gene, which suggests that other molecular mechanisms influence the RARß expression in NSCLC patients. In conclusion, different expression of the RARß gene in SCC and NSCC makes the RARß gene a valuable diagnostic marker for differentiating the NSCLC subtypes.
KeywordsGene expression Lung cancer NSCLC Promoter methylation Retinoid acid receptor-β gene Smoking Tumor suppressor gene
This work was supported by a grant for young scientists of Medical University of Lodz no. 502-03/1-151-03/502-14-142.
Conflicts of Interest
The authors have no conflicts of interest concerning this study.
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