ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Single-Cell Transcriptomics of Pancreatic Cancer Precursors Demonstrates Epithelial and Microenvironmental Heterogeneity as an Early Event in Neoplastic Progression.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 257 papers.
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Who cites it
257 citing papers in PubMed, 400 citations in OpenAlex.
- Addition of Losartan to FOLFIRINOX and Chemoradiation Reduces Immunosuppression-Associated Genes, Tregs, and FOXP3+ Cancer Cells in Locally Advanced Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Integrative single-cell and spatial transcriptomic approaches to decipher the tumor microenvironment and therapeutic resistance in pancreatic cancer.Cancer biology & therapy · 2026Review
- Exercise Modulates Microbial Metabolites and Induces Stromal Remodeling in Pancreatic Cancer.Cancer research · 2026Article
- Myofibroblastic CAF and Malignant Ductal Cell Crosstalk Drives Epithelial-Mesenchymal Transition and Progression in Pancreatic Ductal Adenocarcinoma via THBS2-SDC/Integrin Axes.International journal of molecular sciences · 2026Article
- Tumor-Derived LAMB3 Drives Immunosuppressive LRRC15Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- MYCN-driven metabolic remodelling of the tumour microenvironment in neuroblastoma: implications for stromal biology and CAF heterogeneity.Cancer metastasis reviews · 2026Review
- Cancer-Associated Fibroblasts Promote Epithelial-Mesenchymal Transition and Classical to Basal Subtype Shift in Pancreatic Cancer.Cancer research · 2026Article
- Spatial transcriptomic profiling of ovarian clear cell carcinoma reveals heterogeneity in OXPHOS and EMT gradients.Nature communications · 2026Article
- Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas: current understanding and perspectives on malignant progression.Journal of gastroenterology · 2026Review
- CELF family of RNA-binding proteins: roles in disease biology and potential for therapeutic intervention.Cell communication and signaling : CCS · 2026Review
- Breast cancer immunotherapy: mechanisms of immune evasion, biomarkers, and emerging therapeutic strategies.Molecular cancer · 2026Review
- A bispecific nanobody-drug conjugate targeting TROP2 and c-Met for low-concentration, single-dose treatment of pancreatic cancer.Cell reports. Medicine · 2026Article
- Decoding the CAF-TAM axis: multi-omics dissection and therapeutic targeting of stromal-immune crosstalk in the tumor microenvironment.Cell death & disease · 2026Review
- Benchmarking tools for deciphering cellular crosstalk in spatially-resolved transcriptomics.Genome biology · 2026Article
- Cystic lesions and their role in pancreatic cancer risk stratification.Translational oncology · 2026Review
- Catching pancreatic cancer early: Are we there yet?Journal of the National Cancer Center · 2026Review
- Tumorigenesis and Tumor Microenvironment in Lung Cancer.Current issues in molecular biology · 2026Review
- MicroRNA-146a Protects against Hepatocellular Carcinoma through Suppression of CCL5.Cancer research communications · 2026Article
- Identification and characterization of MARCO-expressing tumor-associated macrophages in pancreatic ductal adenocarcinoma with pan-cancer relevance.NPJ precision oncology · 2026Article
- Immunological and molecular insights into acinar-ductal metaplasia and atypical flat lesions as precursor lesions of pancreatic ductal adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
197 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
Abstract
purposeEarly detection of pancreatic ductal adenocarcinoma (PDAC) remains elusive. Precursor lesions of PDAC, specifically intraductal papillary mucinous neoplasms (IPMNs), represent a EXPERIMENTAL
designSingle-cell RNA sequencing was performed through droplet-based sequencing on 5,403 cells from 2 low-grade IPMNs (LGD-IPMNs), 2 high-grade IPMNs (HGD-IPMN), and 2 PDACs (all surgically resected).
resultsAnalysis of single-cell transcriptomes revealed heterogeneous alterations within the epithelium and the tumor microenvironment during the progression of noninvasive dysplasia to invasive cancer. Although HGD-IPMNs expressed many core signaling pathways described in PDAC, LGD-IPMNs harbored subsets of single cells with a transcriptomic profile that overlapped with invasive cancer. Notably, a proinflammatory immune component was readily seen in low-grade IPMNs, composed of cytotoxic T cells, activated T-helper cells, and dendritic cells, which was progressively depleted during neoplastic progression, accompanied by infiltration of myeloid-derived suppressor cells. Finally, stromal myofibroblast populations were heterogeneous and acquired a previously described tumor-promoting and immune-evading phenotype during invasive carcinogenesis.
conclusionsThis study demonstrates the ability to perform high-resolution profiling of the transcriptomic changes that occur during multistep progression of cystic PDAC precursors to cancer. Notably, single-cell analysis provides an unparalleled insight into both the epithelial and microenvironmental heterogeneities that accompany early cancer pathogenesis and might be a useful substrate to identify targets for cancer interception.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.