4.5 Article

The Prognostic Potential of Human Prostate Cancer-Associated Macrophage Subtypes as Revealed by Single-Cell Transcriptomics

Journal

MOLECULAR CANCER RESEARCH
Volume 19, Issue 10, Pages 1778-1791

Publisher

AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-20-0740

Keywords

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Funding

  1. Hubrecht Institute
  2. Oncode Institute
  3. FP7 MCA-ITN grant agreement [317445]
  4. KWF Dutch Cancer Society [2009-4356]

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Through single-cell transcriptomic analysis of prostate cancer resident macrophages, three distinct populations were identified, with a gene signature highly associated with patient prognosis. This highlights the relevance of tissue-specific macrophage subtypes in the tumor microenvironment for prostate cancer progression.
Macrophages in the tumor microenvironment are causally linked with prostate cancer development and progression, yet little is known about their composition in neoplastic human tissue. By performing single cell transcriptomic analysis of human prostate cancer resident macrophages, three distinct populations were identified in the diseased prostate. Unexpectedly, no differences were observed between macrophages isolated from the tumorous and nontumorous portions of the prostatectomy specimens. Markers associated with canonical M1 and M2 macrophage phenotypes were identifiable, however these were not the main factors defining unique subtypes. The genes selectively associated with each macrophage cluster were used to develop a gene signature which was highly associated with both recurrence- free and metastasis-free survival. These results highlight the relevance of tissue-specific macrophage subtypes in the tumor microenvironment for prostate cancer progression and demonstrates the utility of profiling single-cell transcriptomics in human tumor samples as a strategy to design gene classifiers for patient prognostication.

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