| HRA000433
(Controlled Access)
|
The epigenomic abnormality of pancreatic ductal adenocarcinoma (PDAC) has rarely been investigated due to its strong heterogeneity. Here, we use single-cell multiomics sequencing to simultaneously analyze the DNA methylome, chromatin accessibility, and transcriptome in each individual tumor cell of PDAC patients. We identified normal epithelial cells in the tumor lesion, which have euploid genomes, normal patterns of DNA methylation and chromatin accessibility comparable to those of normal epithelial cells in adjacent normal tissues. We determined that DNA demethylation in cancer cell genome was strongly enriched in heterochromatin regions but depleted in euchromatin regions and observed stronger negative correlations between gene expression and promoter region DNA methylation in cancer cells than in normal epithelial cells. Through integrated analyses, lower expressions of ZNF667 and ZNF667AS1 were identified to connect to poorer prognosis for PDAC patients. |
