The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Experimental microdissection enables functional harmonisation of pancreatic cancer subtypes
Open accessAbstract
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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“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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Cites
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Core Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
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Genomic analyses identify molecular subtypes of pancreatic cancer
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Self-citationWhole genomes redefine the mutational landscape of pancreatic cancer
Initiative, A. P. C. G., Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., et al. (2015) · Nature · doi:10.1038/nature14169 · Cited by 2,642
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Moffitt, R. A., Marayati, R., Flate, E. L., Volmar, K. E., Loeza, S. G. H., Hoadley, K. A., Rashid, N. U., Williams, L. A., Eaton, S. C., Chung, A. H., et al. (2015) · Nature Genetics · doi:10.1038/ng.3398 · Cited by 2,194
Stromal Elements Act to Restrain, Rather Than Support, Pancreatic Ductal Adenocarcinoma
Rhim, A. D., Oberstein, P. E., Thomas, D. H., Mirek, E. T., Palermo, C. F., Sastra, S. A., Dekleva, E. N., Saunders, T., Becerra, C. P., Tattersall, I. W., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.021 · Cited by 2,085
Self-citationPancreatic cancer genomes reveal aberrations in axon guidance pathway genes
Initiative, A. P. C. G., Biankin, A. V., Waddell, N., Kassahn, K. S., Gingras, M.-C., Muthuswamy, L. B., Johns, A. L., Miller, D. K., Wilson, P. J., Patch, A.-M., et al. (2012) · Nature · doi:10.1038/nature11547 · Cited by 2,058
Integrated genomic characterization of pancreatic ductal adenocarcinoma
Raphael, B. J., Hruban, R. H., Aguirre, A. J., Moffitt, R. A., Yeh, J. J., Stewart, C., Robertson, A. G., Cherniack, A. D., Gupta, M., Getz, G., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.07.007 · Cited by 2,019
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Pancreatic cancer: Advances and challenges
Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321
Diversity and biology of cancer-associated fibroblasts
Biffi, G., & Tuveson, D. A. (2021) · Physiological Reviews · doi:10.1152/physrev.00048.2019 · Cited by 1,265
Cross-tissue organization of the fibroblast lineage
Buechler, M. B., Pradhan, R., Krishnamurty, A. T., Cox, C. B., Calviello, A. K., Wang, A. W., Yang, Y. A., Tam, L., Caothien, R. H., Roose‐Girma, M., et al. (2021) · Nature · doi:10.1038/s41586-021-03549-5 · Cited by 1,100
Dominguez, C. X., Müller, S., Keerthivasan, S., Koeppen, H., Hung, J., Gierke, S., Breart, B., Foreman, O., Bainbridge, T. W., Castiglioni, A., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0644 · Cited by 857
Proteogenomic characterization of pancreatic ductal adenocarcinoma
Cao, L., Huang, C., Cui Zhou, D., Hu, Y., Lih, T. M., Savage, S. R., Krug, K., Clark, D. J., Schnaubelt, M., Chen, L., et al. (2021) · Cell · doi:10.1016/j.cell.2021.08.023 · Cited by 578
Metadata
- 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
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2019-01-18
- Volume
- 68
- Issue
- 6
- Pages
- 1034-1043
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- PMC
- PMC6509007
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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