Evolution of ovarian carcinoma cells through peritoneal dissemination ; genome-wide analysis and clinical application.

1)用DNA甲基化抑制物处理39个卵巢癌细胞株和17个原代培养样本，然后用表达芯片筛选出DNA甲基化靶向的卵巢癌基因。这一分析揭示了转化生长因子-β信号通路受全基因组DNA甲基化的调控。2)我们发现转化生长因子-β途径活性在卵巢癌的大网膜转移中上调。然后，我们用小鼠模型证明了转化生长因子-β信号通路的抑制物对卵巢癌的播散性转移有抑制作用。3)我们发现PDL-1在卵巢癌细胞中的表达抑制了CD8+T淋巴细胞的活性，导致免疫逃逸，促进了卵巢癌的腹膜转移。

1) Treatment of 39 ovarian cancer cell lines and 17 primary culture samples with the inhibitor of DNA methylation, followed by expression microarray, identified genes targeted by DNA methylation in ovarian cancer. This analysis revealed TGF-beta signaling pathway is regulated by genome-wide DNA methylation. 2) We found TGF-beta pathway activity is upregulated in the omental metastases of ovarian cancer. Then we demonstrated the inhibitor of TGF-beta signaling pathway is effective against disseminated metastasis of ovarian cancer using a mouse model. 3) We found expression of PDL-1 in ovarian cancer cells suppresses activity of CD8 positive T lymphocytes, causes immune escape, and facilitates peritoneal dissemination of ovarian cancer.