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Spatially Resolved Single-Cell Assessment of Pancreatic Cancer Expression Subtypes Reveals Co-expressor Phenotypes
Hannah L Williams1, Andressa Dias Costa1, Jinming Zhang1
1Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Cancer Research
|December 2, 2022
Summary
Pancreatic cancer (PDAC) shows complex subtypes. A new multiplex immunofluorescence method reveals significant intratumoral heterogeneity, impacting patient outcomes and treatment strategies.
Area of Science:
- Oncology
- Molecular Pathology
- Cancer Biology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is traditionally classified into classical and basal-like subtypes based on bulk RNA measurements.
- Recent studies indicate greater complexity in PDAC transcriptional subtypes than previously understood.
Purpose of the Study:
- To develop a multiplex immunofluorescence (mIF) pipeline for detailed single-cell analysis of PDAC subtypes.
- To investigate the spatial distribution and clinical implications of PDAC intratumoral heterogeneity.
Main Methods:
- Development of a multiplex immunofluorescence (mIF) pipeline to quantify protein expression of six key PDAC subtype markers.
- Single-cell interrogation of PDAC tumors from resection specimens and core needle biopsies.
- Analysis of intratumoral heterogeneity, co-expression patterns, and cell-cell neighbor interactions.
Main Results:
- Striking intratumoral subtype heterogeneity was observed in both primary and metastatic PDAC, associated with patient outcomes.
- Tumor cells co-expressing classical and basal markers were prevalent (>90%) and suggested an intermediate state.
- Intratumoral heterogeneity was reduced in patient-derived organoid cultures compared to tumors.
Conclusions:
- The developed mIF pipeline provides a clinically applicable method for assessing PDAC intratumoral heterogeneity.
- Identified heterogeneity and co-expressor cells may offer insights into PDAC prognosis and inform treatment selection.
- Understanding subtype dynamics is crucial for advancing PDAC patient care.
