Methylation And Function Of PLCD1 In Esophageal Cancer And Its Impact On Quality Of Life And Survival

Objective:To detect the expression,epigenetic alterations and tumor suppressor function of PLCD1 in esophageal cancer and to analyze the association between PLCD1 methylation and survival of esophageal cancer patients.Methods:After the esophageal cancer tissue was collected,the immunohistochemistry and RT-PCR are used to examine the expression of PLCD1 in esophageal cancer tissue,adjacent tissue,and cell lines.The association between PLCD1 expression and histological grade in esophageal cancer was analyzed by the online oncology database.The MSP and BGS were used to determine the epigenetic alterations of PLCD1 in esophageal tumors.Esophageal cancer cell lines treated with pharmacological demethylation AZA and TSA to determine whether PLCD1 silencing was directly mediated by promoter methylation.We investigated the role of PLCD1 methylation and Cofilin-mediated pseudopodia formation and cytoskeletal stability decrease in the invasionand metastasis of esophageal cancer through clinical specimens,cell experiments,and in vivo animal experiments.Results:The expression of PLCD1 was frequent in human normal cell lines and tissues.While in esophageal cancer tissues and cell lines,we found that PLCD1 was silenced or under-expressed.In normal esophageal tissues,no methylation of PLCD1 was detected,while methylation of PLCD1 could be observed in six of nine esophageal cancer cell lines and 76 of 121 primary tumors.Our results showed that esophageal cancer cell proliferation,colony formation and migration ability in vitro and the tumor growth in vivo could be significantly inhibited by PLCD1.However,no significant correlation between survival and the methylation of PLCD1 in esophageal cancer was found.Conclusion:The methylation of PLCD1 is frequently observed in esophageal cancer,and PLCD1 could be a promising biomarker for the diagnosis and treatment of early stage of esophageal cancer,and provide a new theoretical platform for further elucidating the molecular mechanism behind the high degree of malignancy of esophageal cancer.