Integrated single-cell multiomics analysis reveals novel candidate markers for prognosis in human pancreatic ductal adenocarcinoma.
Xiaoying FanPing LuHongwei WangShuhui BianXinglong WuYu ZhangYang LiuDanqi FuLu WenJihui HaoFu-Chou TangPublished in: Cell discovery (2022)
The epigenomic abnormality of pancreatic ductal adenocarcinoma (PDAC) has rarely been investigated due to its strong heterogeneity. Here, we used single-cell multiomics sequencing to simultaneously analyze the DNA methylome, chromatin accessibility and transcriptome in individual tumor cells of PDAC patients. We identified normal epithelial cells in the tumor lesion, which have euploid genomes, normal patterns of DNA methylation, and chromatin accessibility. Using all these normal epithelial cells as controls, we determined that DNA demethylation in the cancer genome was strongly enriched in heterochromatin regions but depleted in euchromatin regions. There were stronger negative correlations between RNA expression and promoter DNA methylation in cancer cells compared to those in normal epithelial cells. Through in-depth integrated analyses, a set of novel candidate biomarkers were identified, including ZNF667 and ZNF667-AS1, whose expressions were linked to a better prognosis for PDAC patients by affecting the proliferation of cancer cells. Our work systematically revealed the critical epigenomic features of cancer cells in PDAC patients at the single-cell level.
Keyphrases
- single cell
- dna methylation
- rna seq
- genome wide
- gene expression
- end stage renal disease
- newly diagnosed
- ejection fraction
- high throughput
- transcription factor
- chronic kidney disease
- dna damage
- endothelial cells
- signaling pathway
- single molecule
- patient reported outcomes
- poor prognosis
- mass spectrometry
- squamous cell carcinoma
- oxidative stress
- papillary thyroid
- optical coherence tomography
- squamous cell
- high speed
- childhood cancer