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Methylation of TFPI-2 is an early event of esophageal carcinogenesis.

ABSTRACT: To explore the epigenetic changes and the function of TFPI-2 in esophageal cancer.Nine esophageal cancer cell lines, nine normal esophageal mucosa, 60 esophageal dysplasia and 106 advanced esophageal cancer samples were included in this study. TFPI-2 methylation was examined by methylation-specific PCR. TFPI-2 expression was evaluated by immunohistochemistry in tissue samples. The effect of TFPI-2 on proliferation, apoptosis, invasion and migration was analyzed by colony formation assay, western blot assay, transwell assay and flow cytometric analysis.TFPI-2 expression was regulated by promoter region hypermethylation in human esophageal cancer cell lines, and TFPI-2 expression is inversely correlated with methylation in primary cancer. Methylation was found in 28.2, 33.3 and 33.3% of grade 1, 2 and 3 esophageal dysplasia, and 67% of primary esophageal cancer, but no methylation was found in normal mucosa. Methylation is significantly related to tumor differentiation. Inhibition of invasion, migration, colony formation and proliferation, and induction of apoptosis occurred with the restoration of TFPI-2 expression in the KYSE70 cell line.TFPI-2 is frequently methylated in esophageal cancer with a progression tendency. TFPI-2 is a potential tumor suppressor in esophageal cancer.

SUBMITTER: Jia Y

PROVIDER: S-EPMC3742137 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Methylation of TFPI-2 is an early event of esophageal carcinogenesis.

Jia Yan Y Yang Yunsheng Y Brock Malcolm V MV Cao Baoping B Zhan Qimin Q Li Yazhuo Y Yu Yuanzi Y Herman James G JG Guo Mingzhou M

Epigenomics 20120401 2

<h4>Aims</h4>To explore the epigenetic changes and the function of TFPI-2 in esophageal cancer.<h4>Materials & methods</h4>Nine esophageal cancer cell lines, nine normal esophageal mucosa, 60 esophageal dysplasia and 106 advanced esophageal cancer samples were included in this study. TFPI-2 methylation was examined by methylation-specific PCR. TFPI-2 expression was evaluated by immunohistochemistry in tissue samples. The effect of TFPI-2 on proliferation, apoptosis, invasion and migration was an ...[more]

PMID: 22449186

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Project description:BACKGROUND:MicroRNAs are dysregulated in colorectal cancer and subsets correlated with advanced tumor stage and metastasis. Data are lacking on microRNA dysregulation from early to late-stage disease. OBJECTIVE:The purpose of this study was to identify a microRNA signature associated with the primary tumor and metastatic site in stage IV disease and to examine whether the signature is evident in earlier stages. DESIGN:A microRNA profile was generated and then explored in normal colon tissue (n = 5), early stage (stage I and II; n = 10), and late-stage (stage III and IV; n = 14) colorectal primary tumors via polymerase chain reaction to delineate molecular events that may promote colorectal carcinogenesis. SETTING:Genome-wide microRNA expression profiling was performed. PATIENTS:A total of 14 patient-matched stage IV primary colorectal cancer tumors and corresponding liver metastases were included. MAIN OUTCOME MEASURES:MicroRNA array technology was used to identify microRNA expression-predictive metastatic potential in the primary tumor. RESULTS:A distinct 9-member signature group of microRNAs was concurrent in stage IV primary colorectal cancer and their corresponding liver metastases, when compared with surrounding unaffected colon and liver tissue (microRNA-18b, microRNA-93, microRNA-182, microRNA-183, microRNA21, microRNA-486-5p, microRNA-500a, microRNA-552, and microRNA-941). Of the microRNA panel, only microRNA486-5p was differentially expressed in early stage colorectal cancer samples compared with normal tissue (p = 0.001) and additionally differentially expressed between late-stage colorectal cancer samples and normal tissue (p < 0.01). LIMITATIONS:Our microRNA profile was generated in a small subset of patients and will require validation in more samples. CONCLUSIONS:We identified a distinct microRNA signature in primary colon and matched metastatic disease. On additional investigation, 1 microRNA was differentially expressed in both early and late-stage cancer patient samples, and it may herald an early event in colorectal carcinogenesis. This study warrants additional investigation with a larger patient cohort to better understand the effect of microRNAs in carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A723.

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Methylation of TFPI-2 is an early event of esophageal carcinogenesis.

Publications

Methylation of TFPI-2 is an early event of esophageal carcinogenesis.

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