S S Zhang1, J J Tan1, L Li2, W T Chen1, N J Han1, S P Guo1, S Zheng2, Y Liu1, Y N Gao1. 1. Department of Etiology and Carcinogenesis, Beijing Key Laboratory of Carcinogenesis and Cancer Prevention, State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China. 2. Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100021, China.
Abstract
OBJECTIVE: To explore the expression of delta-like 1 homolog (DLK1) gene in non-small cell lung cancer (NSCLC) and its regulatory mechanism. METHODS: The expression levels of DLK1 protein in 204 NSCLC tissues were examined by immunohistochemical (IHC) staining, and the correlation between DLK1expression and clinicopathological features was analyzed. Bisulfate sequencing PCR (BSP) of DNA samples from the tumor tissues of 18 NSCLC patients was performed to evaluate the DNA methylation status of CpG island in the DLK1 promoter region, and also compared with the corresponding IHC staining of DLK1 protein in the same samples. RESULTS: Among the 102 squamous cell carcinoma (SCC) tissue specimens and their adjacent normal bronchial epithelia, DLK1 was up-regulated in 72 and 37 samples, respectively (P=0.001), and among 102 adenocarcinomas (ADC) tissues and their adjacent alveolar tissues, DLK1 was up-regulated in 77 and 7 samples, respectively (P<0.001). In addition, overexpression of DLK1 was significantly associated with histological type, clinical stage and tumor size of NSCLC (P<0.05 for all). The expression of DLK1protein was inversely correlated with its promoter methylation (P<0.05). CONCLUSION: DLK1 expression is up-regulated in NSCLCs, which may be due, at least in part, to the DNA hypomethylation in the promoter region of theDLK1 gene.
OBJECTIVE: To explore the expression of delta-like 1 homolog (DLK1) gene in non-small cell lung cancer (NSCLC) and its regulatory mechanism. METHODS: The expression levels of DLK1 protein in 204 NSCLC tissues were examined by immunohistochemical (IHC) staining, and the correlation between DLK1expression and clinicopathological features was analyzed. Bisulfate sequencing PCR (BSP) of DNA samples from the tumor tissues of 18 NSCLCpatients was performed to evaluate the DNA methylation status of CpG island in the DLK1 promoter region, and also compared with the corresponding IHC staining of DLK1 protein in the same samples. RESULTS: Among the 102 squamous cell carcinoma (SCC) tissue specimens and their adjacent normal bronchial epithelia, DLK1 was up-regulated in 72 and 37 samples, respectively (P=0.001), and among 102 adenocarcinomas (ADC) tissues and their adjacent alveolar tissues, DLK1 was up-regulated in 77 and 7 samples, respectively (P<0.001). In addition, overexpression of DLK1 was significantly associated with histological type, clinical stage and tumor size of NSCLC (P<0.05 for all). The expression of DLK1protein was inversely correlated with its promoter methylation (P<0.05). CONCLUSION:DLK1 expression is up-regulated in NSCLCs, which may be due, at least in part, to the DNA hypomethylation in the promoter region of theDLK1 gene.