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Pan-cancer and single-cell analyses identify CD44 as an immunotherapy response predictor and regulating macrophage

Qian Zhang1,2, Xinyu Wang2, Yang Liu3

  • 1College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning, China.

Frontiers in Oncology
|April 9, 2024
PubMed
Summary

Cluster of differentiation (CD) 44, a cell surface glycoprotein, is elevated in most cancers and linked to poor prognosis. Its knockdown inhibits tumor growth and M2 macrophage polarization, suggesting therapeutic potential.

Keywords:
CD44colorectal (colon) cancerimmunotherapymacrophagespan cancer

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Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Cluster of differentiation (CD) 44 is a cell surface glycoprotein crucial for tumor progression.
  • Understanding CD44's role in various cancers and its immune interactions is vital for therapeutic development.

Purpose of the Study:

  • To systematically analyze the expression, genomic alterations, and immune characteristics of CD44 across 33 cancer types.
  • To investigate CD44's impact on tumor development, macrophage polarization, and response to immunotherapy.

Main Methods:

  • Comprehensive analysis of CD44 expression and genomic alterations using TIMER2.0 and CIBERSORT.
  • Single-cell transcriptional landscape examination and Pseudotime trajectory analysis.
  • In vitro knockdown experiments in colorectal cancer cells and macrophages.

Main Results:

  • CD44 expression is elevated in most cancers, correlating with unfavorable prognosis and immune cell infiltration.
  • CD44+ monocytes exhibit higher information flow; CD44 predicts response to immune checkpoint blockade.
  • CD44 knockdown inhibited colorectal cancer cell proliferation and M2 macrophage polarization.

Conclusions:

  • CD44 plays a significant role in tumor development and macrophage polarization.
  • CD44 holds predictive value for clinical prognosis and immunotherapy response.