Pan-cancer and single-cell analyses identify CD44 as an immunotherapy response predictor and regulating macrophage polarization and tumor progression in colorectal cancer

Qian Zhang; Xinyu Wang; Yang Liu; Hao Xu; Chun Ye

doi:10.3389/fonc.2024.1380821

Pan-cancer and single-cell analyses identify CD44 as an immunotherapy response predictor and regulating macrophage polarization and tumor progression in colorectal cancer

Front Oncol. 2024 Mar 25:14:1380821. doi: 10.3389/fonc.2024.1380821. eCollection 2024.

Authors

Qian Zhang^{1

2}, Xinyu Wang², Yang Liu³, Hao Xu², Chun Ye²

Affiliations

¹ College of Medicine and Biological Information Engineering, Northeastern University, Shenyang, Liaoning, China.
² Department of General Surgery, General Hospital of Northern Theater Command, Shenyang, China.
³ Department of Pharmacy, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China.

Abstract

Introduction: Cluster of differentiation (CD) 44 is a non-kinase cell surface transmembrane glycoprotein critical for tumor maintenance and progression.

Methods: We conducted a systematic analysis of the expression profile and genomic alteration profile of CD44 in 33 types of cancer. The immune characteristics of CD44 were comprehensively explored by TIMER2.0 and CIBERSORT. In addition, the CD44 transcriptional landscape was examined at the single-cell level. Then, Pseudotime trajectory analysis of CD44 gene expression was performed using Monocle 2, and CellChat was utilized to compare the crosstalk differences between CD44⁺monocytes and CD44^- monocytes. Tumor immune dysfunction and exclusion (TIDE) was used to evaluate the predictive ability of CD44 for immune checkpoint blockade (ICB) responses. The effects of CD44 on colorectal cancer (CRC) and macrophage polarization were investigated by knocking down the expression of CD44 in HCT-116 cell and macrophages in vitro.

Results: The expression of CD44 elevated in most cancers, predicting unfavorable prognosis. In addditon, CD44 was correlation with immune cell infiltration and key immune regulators. CD44⁺ monocytes had a higher information flow intensity than CD44- monocytes. CD44 had good predictive ability for immune checkpoint blockade responses. Knockdown of CD44 inhibited the proliferation, migration, and invasion of HCT-116 cell in vitro. Knockdown of CD44 inhibited M2 macrophage polarization.

Discussion: These findings suggest that CD44 is involved in regulating tumor development, macrophage polarization, and has certain predictive value for patient clinical prognosis and response to immunotherapy.

Keywords: CD44; colorectal (colon) cancer; immunotherapy; macrophages; pan cancer.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Liaoning Science and Technology Project Mechanism and clinical application of thrombin activated plasminogen activator inhibitor (TAFI) in the invasion and metastasis of gastric cancer (2022JH2/101500033).