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2000
Volume 32, Issue 19
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Colorectal cancer (CRC) cases with advanced or distal metastases experience a survival rate of less than 20%, with the lack of spectral therapeutic targets and prognostic markers posing a significant challenge for CRC treatment. may be a CRC-targeted therapy for which there is currently inadequate evidence.

Aim

In this report, we performed a comprehensive analysis of data on colorectal cancer (CRC) to elucidate the association among Solute Carrier Family 4 Member 4 () and the abundance of immunological features and immune cell infiltration in CRC and to explore the impact of SLC4A4 on the CRC tumor microenvironment.

Objective

The objective of this study was to systematically reveal the characteristics of the tumor microenvironment created by .

Methods

We downloaded RNA sequencing files from the Cancer Genome Atlas (TCGA-COADREAD). The correlations of SLC4A4 with immune-related characteristics were analyzed. A Limma package was applied for selecting /immunity-related differentially expressed genes (DEGs). An assessment system for predicting CRC prognosis was constructed based on univariate COX and multivariate COX analyses. A nomogram was also designed to assess the survival risk status of CRC. Besides, we evaluated the potential association of to immunotherapy through TIDE analysis.

Results

We found that expression was positively correlated with immune checkpoint expression (). promoted the infiltration of CD8 T cells, dendritic cells, macrophages, NK cells, and Th1 cells in CRC, shaping the inflammatory tumor microenvironment. Up-regulated might improve drug response to anti- therapy, anti- therapy, nivolumab, and ipilimumab in CRC patients, and down-regulated might promote drug response to anti-EGFR therapy and Aflibercept drug response. The constructed RiskScore model showed excellent predictive effect and robustness. RiskScore presented a trend of negative correlation with , which was consistent with the trend of the effect of on CRC survival. TIDE analysis further disclosed that high-risk groups with high levels of SLC4A4 were possible for immune escape. Finally, the constructed nomogram also showed potential clinical value.

Conclusion

Overall, upregulation of expression promoted an inflammatory tumor microenvironment in CRC, and RiskScore predicted therapeutic expectancy. could be a potentially clinically valuable target for CRC therapy.

© 2025 Bentham Science Publishers
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/content/journals/cmc/10.2174/0109298673277357231218070812
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SLC4A4 Moulds the Inflammatory Tumor Microenvironment and Predicts Therapeutic Expectations in Colorectal Cancer
Curr. Med. Chem. 32, 3861 (2025); https://doi.org/10.2174/0109298673277357231218070812
/content/journals/cmc/10.2174/0109298673277357231218070812
/content/journals/cmc/10.2174/0109298673277357231218070812
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  • Article Type:     Research Article
Keyword(s): Colorectal cancer; CRC therapy; immunogenicity; immunotherapy; prognosis; SLC4A4

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