Single-cell transcriptomics reveals heterogeneous progression and EGFR activation in pancreatic adenosquamous carcinoma
| Autor: | Zhe Liu, Jialei Zhai, Han Li, Junming Xu, Jiantao Kou, Xinxue Zhang, Zhiwei Ji, Xin Zhao, Ren Lang, Huaguang Wang, Hua Fan, Zhigang Zhang, Qiang He, Lixin Li, Shaocheng Lyu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Stromal cell
Myeloid DNA Copy Number Variations Cell pancreatic cancer Pancreatic Adenosquamous Carcinoma Biology Applied Microbiology and Biotechnology pancreatic adenosquamous carcinoma single-cell RNA sequencing Carcinoma Adenosquamous Genetic Heterogeneity Pancreatic cancer medicine Biomarkers Tumor Humans Molecular Biology Ecology Evolution Behavior and Systematics cell-cell communication Intraductal papillary mucinous neoplasm Chemotactic Factors Sequence Analysis RNA S100 Proteins intraductal papillary mucinous neoplasm Cell Biology medicine.disease Adenocarcinoma Mucinous Neoplasm Proteins ErbB Receptors Pancreatic Neoplasms medicine.anatomical_structure Cancer cell Cancer research heterogeneity Single-Cell Analysis Pancreas Transcriptome Developmental Biology Research Paper |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| Popis: | Pancreatic adenosquamous carcinoma (PASC) - a rare pathological pancreatic cancer (PC) type - has a poor prognosis due to high malignancy. To examine the heterogeneity of PASC, we performed single-cell RNA sequencing (scRNA-seq) profiling with sample tissues from a healthy donor pancreas, an intraductal papillary mucinous neoplasm, and a patient with PASC. Of 9,887 individual cells, ten cell subpopulations were identified, including myeloid, immune, ductal, fibroblast, acinar, stellate, endothelial, and cancer cells. Cancer cells were divided into five clusters. Notably, cluster 1 exhibited stem-like phenotypes expressing UBE2C, ASPM, and TOP2A. We found that S100A2 is a potential biomarker for cancer cells. LGALS1, NPM1, RACK1, and PERP were upregulated from ductal to cancer cells. Furthermore, the copy number variations in ductal and cancer cells were greater than in the reference cells. The expression of EREG, FCGR2A, CCL4L2, and CTSC increased in myeloid cells from the normal pancreas to PASC. The gene sets expressed by cancer-associated fibroblasts were enriched in the immunosuppressive pathways. We demonstrate that EGFR-associated ligand-receptor pairs are activated in ductal-stromal cell communications. Hence, this study revealed the heterogeneous variations of ductal and stromal cells, defined cancer-associated signaling pathways, and deciphered intercellular interactions following PASC progression. |
| Databáze: | OpenAIRE |
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