# Expression and Clinical Significance of CD47 in Colorectal Cancer: A Review

**Authors:** Qijie Li, Paola Vignali, Donghao Tang, Giulia Martinelli, Beatrice Fuochi, Rebecca Sparavelli, Anello Marcello Poma, Rossella Bruno, Elisabetta Macerola, Clara Ugolini

PMC · DOI: 10.3390/cancers18010054 · Cancers · 2025-12-24

## TL;DR

This paper reviews the role of CD47 in colorectal cancer, exploring its potential as a biomarker and therapeutic target for improved immunotherapy.

## Contribution

The paper synthesizes findings on CD47 expression and its clinical implications in colorectal cancer, emphasizing the need for standardized evaluation methods.

## Key findings

- CD47 is overexpressed in colorectal cancer, particularly in CMS1 and CMS4 subtypes.
- High CD47 levels correlate with advanced cancer stages and poor prognosis in some studies.
- CD47 co-expresses with immune checkpoints and oncogenic pathways, suggesting a role in immune evasion.

## Abstract

Colorectal cancer is one of the most common and deadly cancers worldwide. Despite advances in treatment, many patients still experience relapse or poor outcomes, highlighting the need for new immune-based strategies. One promising target is CD47, a molecule on tumor cells that sends a “don’t eat me” signal to immune cells and helps cancer escape immune destruction. However, previous studies have reported inconsistent CD47 expression levels, making its clinical interpretation challenging. This review explores what is currently known about CD47 expression in colorectal cancer, how it interacts with the immune environment, and how it relates to patient prognosis and molecular subtypes. By bringing together findings from different studies, we aim to clarify the potential of CD47 as a biomarker and therapeutic target, providing insights that may support the development of more effective and personalized immunotherapy approaches for colorectal cancer.

Cluster of Differentiation 47 (CD47), an innate immune checkpoint, facilitates immune escape by binding signal regulatory protein alpha (SIRPα) to inhibit macrophage phagocytosis. Its significance in colorectal cancer (CRC) has garnered heightened interest. This review summarizes five immunohistochemistry (IHC) studies and complementary transcriptomic analyses assessing CD47 in CRC. IHC results consistently indicated membrane overexpression, though positivity rates varied widely (16–91%) due to methodological heterogeneity. Transcriptomic results confirmed CD47 upregulation, especially in Consensus Molecular Subtype 1 (CMS1) and CMS4 subtypes and revealed co-expression with immune checkpoints and oncogenic pathways. Clinically, high CD47 levels were associated with advanced TNM stage, metastasis, poor differentiation, and altered immune infiltration; however, the prognostic significance varied among cohorts. Overall, CD47 appears to be a promising biomarker and therapeutic target, but clinical translation requires standardized evaluation, including harmonized antibody selection and scoring cut-offs, and prospective validation.

## Linked entities

- **Genes:** CD47 (CD47 molecule) [NCBI Gene 961]
- **Proteins:** CD47 (CD47 molecule), SIRPA (signal regulatory protein alpha)
- **Diseases:** colorectal cancer (MONDO:0005575), CRC (MONDO:0005575)

## Full-text entities

- **Genes:** SIRPA (signal regulatory protein alpha) [NCBI Gene 140885] {aka BIT, CD172A, MFR, MYD-1, MYD1, P84}
- **Diseases:** CRC (MESH:D015179), metastasis (MESH:D009362)

## Full text

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## Figures

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## References

120 references — full list in the complete paper: https://tomesphere.com/paper/PMC12784865/full.md

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Source: https://tomesphere.com/paper/PMC12784865