Integrated single-cell multiomics analysis reveals novel candidate markers for prognosis in human pancreatic ductal adenocarcinoma

Cell Discovery

Ping Lu¹  Lu Wen¹  Yu Zhang²  Fuchou Tang³  Shuhui Bian⁴  Xinglong Wu⁵  Xiaoying Fan⁶  Danqi Fu⁷  Yang Liu⁷  Jihui Hao⁷  Hongwei Wang⁷ 

[1] Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University, Beijing, China;Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University, Beijing, China;Biomedical Pioneering Innovation Center, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing, China;Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University, Beijing, China;Biomedical Pioneering Innovation Center, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing, China;Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China;Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University, Beijing, China;Biomedical Pioneering Innovation Center, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing, China;State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, China;Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University, Beijing, China;College of Animal Science and Technology, Hebei Agricultural University, Baoding, Hebei, China;Beijing Advanced Innovation Center for Genomics (ICG), School of Life Sciences, Peking University, Beijing, China;The Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China;Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China;

DOI  :  10.1038/s41421-021-00366-y

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY