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Elucidation of Tumor-Stromal Heterogeneity and the Ligand-Receptor Interactome by Single-Cell Transcriptomics in Real-world Pancreatic Cancer Biopsies
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Abstract
Purpose: Precision medicine approaches in pancreatic ductal adenocarcinoma (PDAC) are imperative for improving disease outcomes. With molecular subtypes of PDAC gaining relevance in the context of therapeutic stratification, the ability to characterize heterogeneity of cancer-specific gene expression patterns is of great interest. In addition, understanding patterns of immune evasion within PDAC is of importance as novel immunotherapeutic strategies are developed. Experimental Design: Single-cell RNA sequencing (scRNA-seq) is readily applicable to limited biopsies from human primary and metastatic PDAC and identifies most cancers as being an admixture of previously described epithelial transcriptomic subtypes. Results: Integrative analyses of our data provide an in-depth characterization of the heterogeneity within the tumor microenvironment, including cancer-associated fibroblast subclasses, and predicts for a multitude of ligand-receptor interactions, revealing potential targets for immunotherapy approaches. Conclusions: Our analysis demonstrates that the use of de novo biopsies from patients with PDAC paired with scRNA-seq may facilitate therapeutic prediction from limited biopsy samples.
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“scRNA-seq datasets from human and murine tumors have identified multiple unique neoplastic epithelial populations within individual tumors149,269, which represent multiple PDAC subtypes within the same tumor270.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [269]
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Metadata
- Authors
- Lee, J. J., Bernard, V., Semaan, A., Monberg, M. E., Huang, J., Stephens, B. M., Lin, D., Rajapakshe, K. I., Weston, B. R., Bhutani, M. S., Haymaker, C. L., Bernatchez, C., Taniguchi, C. M., Maitra, A., & Guerrero, P. A.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Maitra, Anirban
- Guerrero, Paola A.
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2021-08-23
- Volume
- 27
- Issue
- 21
- Pages
- 5912-5921
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- PMC
- PMC8563410
- OpenAlex
- W3195783449
- Cited by
- 128
- References
- 64
- Citations by year
- 2026: 17 · 2025: 30 · 2024: 21 · 2023: 23 · 2022: 28 · 2021: 5
- FWCI
- 7.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Cancer Research (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Research Square (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (U01CA196403, U01CA200468, P50CA221707, R01CA227518-01A1, U54CA096300, U54CA096297, T32CA217789, T32CA009599)
- Cancer Prevention and Research Institute of Texas (CPRIT RR140012, SE-2616/2-1)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- pancreatic ductal adenocarcinoma, tumor heterogeneity, tumor microenvironment, cancer-associated fibroblasts, ligand-receptor interactions, immune evasion, immunotherapy targets, molecular subtypes, metastatic pancreatic cancer, single-cell transcriptomics
- MeSH terms
- Exome Sequencing, Biopsy, Humans, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal, Tumor Microenvironment, Transcriptome
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