Cited by 128Pancreatic and Hepatic Oncology ResearchSingle-cell and spatial transcriptomicsCancer Genomics and Diagnostics

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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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Lee, Jaewon J., Bernard, Vincent, Semaan, Alexander, Monberg, Maria E., Huang, Jonathan, Stephens, Bret M., Lin, Daniel, Rajapakshe, Kimal I., Weston, Brian R., Bhutani, Manoop S., Haymaker, Cara L., Bernatchez, Chantale, Taniguchi, Cullen M., Maitra, Anirban, Guerrero, Paola A.·2021·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-20-3925PMC PMC8563410

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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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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: Lee, Jaewon J.
Bernard, Vincent
Semaan, Alexander
Monberg, Maria E.
Huang, Jonathan
Stephens, Bret M.
Lin, Daniel
Rajapakshe, Kimal I.
Weston, Brian R.
Bhutani, Manoop S.
Haymaker, Cara L.
Bernatchez, Chantale
Taniguchi, Cullen M.
Maitra, Anirban
Guerrero, Paola A.
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2021-08-23
Volume: 27
Issue: 21
Pages: 5912-5921
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-20-3925
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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Elucidation of Tumor-Stromal Heterogeneity and the Ligand-Receptor Interactome by Single-Cell Transcriptomics in Real-world Pancreatic Cancer Biopsies

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