Abstract
Abstract Esophageal cancer ranks as the sixth most deadly cancer and esophageal squamous cell carcinoma (ESCC) is the sixth most common cause of cancer deaths in males in worldwide. Therefore, it is important to identify molecular markers for clinical diagnosis. Homeodomain-only protein X (HOPX)-β is a tumor suppressor gene and its promoter methylation is shown to be frequent in human cancer. Mucin 1 (MUC1) is a transmembrane mucin that is highly expressed in various cancers and correlates with malignant potential. In addition, the degree of whole genome methylation decreases as the lesion progressing from a benign proliferation of cells to an invasive cancer. The aim of this study was to investigate HOPX-β and MUC1 promoter methylation status and global methylation level in different stages of ESCC patients. Methylation-specific PCR (MSP) revealed that the methylation rate of HOPX-β was 26.5% (27/102) in tumor samples and only 9% (9/100) in paired non-tumor samples (p<0.05). In HOPX-β promoter hypermethylation samples, the frequency of lymph node invasion and tumor metastasis was increased about 3-fold and 2-fold, respectively. Furthermore, HOPX-β promoter methylation frequency was increased about 3-fold in advanced stage. On the other hand, the methylation frequency of MUC1 was 90.7% (97/107) in paired non-tumor samples while the methylation frequency was decreased to 53.3% (57/107) in tumor samples. 78.5% (84/107) of tumor samples showed significantly decline in the degree of methylation compared with paired non-tumor samples (p<0.0001). We found a decrease tendency in methylation frequency of MUC1 correlated with clinical stage (early/advanced), the frequency of lymph node invasion and metastasis. Importantly, the methylation rate of MUC1 was inversely related with the tumor size (p=0.0105). The level of global long interspersed nuclear element 1 (LINE-1) methylation in ESCC tissues (mean 65.8%) was significantly lower than paired non-tumor samples (mean 79.5%). However, there is no relation between the level of global LINE-1 methylation and tumor stage or survival rate. Our findings indicate that LINE-1, MUC1 methylation level and HOPX-β hypermethylation in ESCC are useful markers in clinical diagnosis. Citation Format: Yu Chun Kao, Sheng Hsiung Lin, Chun Chieh Yu, Ruei Nian Li, Ming Tsang Wu. Aberrant promoter methylation of HOPX-β, MUC1 genes and global methylation in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr C12.
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