KEY TAKEAWAYS
- The study aimed to investigate the molecular characteristics of distinct clusters of neoplastic epithelial cells in TME of pancreatic cancer pts.
- Researchers noticed a comprehensive landscape of pancreatic cancer and fibroblast populations by unveiling potential therapeutic targets.
Recent single-cell transcriptomic analyses have identified distinct clusters of neoplastic epithelial cells and cancer-associated fibroblasts within the pancreatic cancer tumor microenvironment (TME). However, these clusters’ molecular characteristics and biological significance still need to be clarified, hindered by intra- and inter-tumoral heterogeneity challenges.
Seongryong Kim and her team aimed to address these knowledge gaps by undertaking an integrative analysis.
Researchers performed an inclusive analysis by conducting single-cell RNA sequencing on enriched non-immune cell populations obtained from 17 pancreatic tumor tissues (comprising 16 pancreatic cancer and one high-grade dysplasia). Additionally, paired spatial transcriptomic data were generated from 7 patient samples, providing a comprehensive dataset for investigating neoplastic epithelial cells and cancer-associated fibroblasts in the pancreatic TME.
The study identified 5 distinct functional subclusters within pancreatic cancer cells and 6 distinct subclusters of cancer-associated fibroblasts. Through in-depth profiling of their characteristics, it was observed that these subclusters effectively deconvoluted the majority of features suggested in bulk transcriptome analysis of pancreatic cancer. A novel cancer cell subcluster, Ep_VGLL1, was identified, displaying intermediate characteristics between the extremities of the basal-like and classical dichotomy. This subcluster demonstrated prognostic value, with its molecular features suggesting transitional properties between the basal-like and classical subtypes. This finding was further supported by spatial transcriptomic data.
The study concluded by analyzing a comprehensive landscape of pancreatic cancer and fibroblast populations, introducing novel insights into the dynamic states of pancreatic cancer cells. Additionally, the research unveiled potential therapeutic targets, marking a significant step toward advancing treatment strategies for this complex disease.
The study is sponsored by National Research Foundation and Daewoong foundation
Source: https://pubmed.ncbi.nlm.nih.gov/38297291/
Kim S, Leem G, Choi J, et al.” Integrative analysis of spatial and single-cell transcriptome data from human pancreatic cancer reveals an intermediate cancer cell population associated with poor prognosis. Genome Med. 2024 Jan 31;16(1):20. doi: 10.1186/s13073-024-01287-7. PMID: 38297291; PMCID: PMC10832111.
