Cited by 220Pancreatic and Hepatic Oncology ResearchGene expression and cancer classificationCancer Genomics and Diagnostics

Experimental microdissection enables functional harmonisation of pancreatic cancer subtypes

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Maurer, Carlo, Holmstrom, Sam R, He, Jing, Laise, Pasquale, Su, Tao, Ahmed, Aqeel, Hibshoosh, Hanina, Chabot, John A +8 more·2019·Gut

Abstract

Objective: Pancreatic ductal adenocarcinoma (PDA) has among the highest stromal fractions of any cancer and this has complicated attempts at expression-based molecular classification. The goal of this work is to profile purified samples of human PDA epithelium and stroma and examine their respective contributions to gene expression in bulk PDA samples. Design: We used laser capture microdissection (LCM) and RNA sequencing to profile the expression of 60 matched pairs of human PDA malignant epithelium and stroma samples. We then used these data to train a computational model that allowed us to infer tissue composition and generate virtual compartment-specific expression profiles from bulk gene expression cohorts. Results: Our analysis found significant variation in the tissue composition of pancreatic tumours from different public cohorts. Computational removal of stromal gene expression resulted in the reclassification of some tumours, reconciling functional differences between different cohorts. Furthermore, we established a novel classification signature from a total of 110 purified human PDA stroma samples, finding two groups that differ in the extracellular matrix-associated and immune-associated processes. Lastly, a systematic evaluation of cross-compartment subtypes spanning four patient cohorts indicated partial dependence between epithelial and stromal molecular subtypes. Conclusion: Our findings add clarity to the nature and number of molecular subtypes in PDA, expand our understanding of global transcriptional programmes in the stroma and harmonise the results of molecular subtyping efforts across independent cohorts.

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Crossref · 10.1136/gutjnl-2018-317706

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  • Mauer et al. found that isolated epithelial tissues supported the Moffitt classical or basal-like subtypes, with no evidence of Bailey ADEX or Collisson exocrine-like subtypes in epithelial-enriched tumor samples.

    “Mauer et al., found isolated epithelial tissues supported the Moffitt “classical” or “basal-like” subtypes, while they found no evidence of the Bailey “ADEX” subtype or Collisson “exocrine-like” subtypes in epithelial enriched tumor samples132.”

    From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [132]

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Authors
Maurer, C., Holmstrom, S. R., He, J., Laise, P., Su, T., Ahmed, A., Hibshoosh, H., Chabot, J. A., Oberstein, P. E., Sepulveda, A. R., Genkinger, J. M., Zhang, J., Iuga, A. C., Bansal, M., Califano, A., & Olive, K. P.
Affiliations
  • Columbia University Irving Medical Center (US)
  • NYU Langone Health (US)
  • University of California San Diego (US)
  • Psychogenics (United States) (US)
Corresponding author
Califano, Andrea
Venue
Gut
Publisher
BMJ
Published
2019-01-18
Volume
68
Issue
6
Pages
1034-1043
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
OpenAlex
W2910033560
Cited by
216
References
27
Citations by year
2026: 15 · 2025: 27 · 2024: 30 · 2023: 22 · 2022: 36 · 2021: 43 · 2020: 27 · 2019: 16
FWCI
12.85
Type
journal article
Language
en
Open access
Locations
  • Gut (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
Keywords
pancreatic ductal adenocarcinoma, tumor stroma, molecular subtypes, stromal gene expression, extracellular matrix, antitumor immunity
MeSH terms
Adenocarcinoma, Computer Simulation, Extracellular Matrix, Humans, Pancreatic Neoplasms, Sensitivity and Specificity, Gene Expression Regulation, Neoplastic, Case-Control Studies, Gene Expression Profiling, Carcinoma, Pancreatic Ductal, Microdissection

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