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Updated: May 23, 2026

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Published on: December 23, 2022
Methylation of TFPI-2 is an early event of esophageal carcinogenesis
Yan Jia1, Yunsheng Yang, Malcolm V Brock
1Department of Gastroenterology & Hepatology, Chinese People's Liberation Army General Hospital, 28 Fuxing Road, Beijing 100853, China.
Aims:
To explore the epigenetic changes and the function of TFPI-2 in esophageal cancer.
Materials & Methods:
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.
Results:
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.
Conclusion:
TFPI-2 is frequently methylated in esophageal cancer with a progression tendency. TFPI-2 is a potential tumor suppressor in esophageal cancer.
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