4.7 Article

Single-cell transcriptomics reveals heterogeneous progression and EGFR activation in pancreatic adenosquamous carcinoma

Journal

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 17, Issue 10, Pages 2590-2605

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/ijbs.58886

Keywords

pancreatic adenosquamous carcinoma; single-cell RNA sequencing; intraductal papillary mucinous neoplasm; heterogeneity; cell-cell communication; pancreatic cancer

Funding

  1. Capital's Funds for Health Improvement and Research, Beijing, PR China [CFH 2020-2-2036]
  2. National Science Foundation of Zhejiang province, Zhejiang, PR China [LY20F020003]
  3. Beijing Municipal Administration of Hospitals Incubating Program, Beijing, PR China [PZ2021003]

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The study used single-cell RNA sequencing to reveal the heterogeneity of pancreatic adenosquamous carcinoma (PASC), identifying cell clusters, potential biomarkers, and intercellular interactions, while defining associated signaling pathways.
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.

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