University of Oulu

Hannah L. Williams, Andressa Dias Costa, Jinming Zhang, Srivatsan Raghavan, Peter S. Winter, Kevin S. Kapner, Scott P. Ginebaugh, Sara A. Väyrynen, Juha P. Väyrynen, Chen Yuan, Andrew W. Navia, Junning Wang, Annan Yang, Timothy L. Bosse, Radha L. Kalekar, Kristen E. Lowder, Mai Chan Lau, Dalia Elganainy, Vicente Morales-Oyarvide, Douglas A. Rubinson, Harshabad Singh, Kimberly Perez, James M. Cleary, Thomas E. Clancy, Jiping Wang, Joseph D. Mancias, Lauren K. Brais, Emma R. Hill, Margaret M. Kozak, David C. Linehan, Richard F. Dunne, Daniel T. Chang, Albert C. Koong, Aram F. Hezel, William C. Hahn, Alex K. Shalek, Andrew J. Aguirre, Jonathan A. Nowak, Brian M. Wolpin; Spatially Resolved Single-Cell Assessment of Pancreatic Cancer Expression Subtypes Reveals Co-expressor Phenotypes and Extensive Intratumoral Heterogeneity. Cancer Res 1 February 2023; 83 (3): 441–455.

Spatially-resolved single-cell assessment of pancreatic cancer expression subtypes reveals co-expressor phenotypes and extensive intra-tumoral heterogeneity

Saved in:
Author: Williams, Hannah L.1; Dias Costa, Andressa1; Zhang, Jinming1;
Organizations: 1Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
2Broad Institute of MIT and Harvard, Cambridge, Massachusetts
3Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts
4Institute for Medical Engineering and Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts
5Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland
6Department of Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts
7Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts
8Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
9Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
10Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California
11Department of Surgery, University of Rochester Medical Center, Rochester, New York
12Department of Medicine, Division of Hematology and Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York
13Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
14Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
Format: article
Version: accepted version
Access: embargoed
Persistent link:
Language: English
Published: American Association for Cancer Research, 2023
Publish Date: 2024-02-03


Pancreatic ductal adenocarcinoma (PDAC) has been classified into classical and basal-like transcriptional subtypes by bulk RNA measurements. However, recent work has uncovered greater complexity to transcriptional subtypes than was initially appreciated using bulk RNA expression profiling. To provide a deeper understanding of PDAC subtypes, we developed a multiplex immunofluorescence (mIF) pipeline that quantifies protein expression of six PDAC subtype markers (CLDN18.2, TFF1, GATA6, KRT17, KRT5, and S100A2) and permits spatially resolved, single-cell interrogation of pancreatic tumors from resection specimens and core needle biopsies. Both primary and metastatic tumors displayed striking intratumoral subtype heterogeneity that was associated with patient outcomes, existed at the scale of individual glands, and was significantly reduced in patient-derived organoid cultures. Tumor cells co-expressing classical and basal markers were present in > 90% of tumors, existed on a basal-classical polarization continuum, and were enriched in tumors containing a greater admixture of basal and classical cell populations. Cell–cell neighbor analyses within tumor glands further suggested that co-expressor cells may represent an intermediate state between expression subtype poles. The extensive intratumoral heterogeneity identified through this clinically applicable mIF pipeline may inform prognosis and treatment selection for patients with PDAC.

see all

Series: Cancer research
ISSN: 0008-5472
ISSN-E: 1538-7445
ISSN-L: 0008-5472
Volume: 83
Issue: 3
Pages: 441 - 455
DOI: 10.1158/0008-5472.CAN-22-3050
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: The Hale Family Center for Pancreatic Cancer Research, Lustgarten Foundation Dedicated Laboratory program, NIH grant U01 CA210171, NIH grant P50 CA127003, Stand Up To Cancer - Lustgarten Foundation Pancreatic Cancer Dream Team Research Grant (Grant Number: SU2C-AACR-DT-20-16a), Pancreatic Cancer Action Network, Noble Effort Fund, Wexler Family Fund, Promises for Purple, and Bob Parsons Fund to B.M. Wolpin. The Hale Family Center for Pancreatic Cancer Research, Lustgarten Foundation Dedicated Laboratory program, NIH grants P50 CA127003, R01 CA248857, R01 CA205406, R01 CA169141, R35 CA197735, and U01 CA250549 to J.A. Nowak. William Raveis Charitable Fund Physician-Scientist of the Damon Runyon Cancer Research Foundation (PST-15–18) to H. Singh. W.C. Hahn is a consultant for ThermoFisher, Solasta Ventures, MPM Capital, KSQ Therapeutics, Tyra Biosciences, Jubilant Therapeutics, RAPPTA Therapeutics, Function Oncology, Riva Therapeutics, Frontier Medicines and Calyx. The indicated Stand Up To Cancer research grant is administered by the American Association for Cancer Research, the Scientific Partner of Stand Up To Cancer.
Copyright information: © 2022 American Association for Cancer Research.