Identification of T cell dysfunction molecular subtypes and exploration of potential immunotherapy targets in BRAF V600E-mutant colorectal cancer

Background Immunotherapy is an effective treatment for BRAF V600E-mutant colorectal cancer, but currently, only a few benefit from it. Therefore, exploring new immunotherapy strategies is essential. Methods We obtained RNA sequencing data and clinical information of colorectal cancer patients from t...

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Veröffentlicht in:Discover. Oncology Jg. 16; H. 1; S. 163 - 20
Hauptverfasser: Gu, Tiefeng, Qi, Haonan, Wang, Jiaqi, Sun, Liangwei, Su, Yongqi, Hu, Hanqing
Format: Journal Article
Sprache:Englisch
Veröffentlicht: New York Springer US 12.02.2025
Springer Nature B.V
Springer
Schlagworte:
Algorithms
Analysis
BRAF V600E
Cancer Research
Colorectal cancer
Datasets
Gene expression
IDO1
Immunotherapy
Internal Medicine
Lymphocytes
Machine learning
Medical prognosis
Medicine
Medicine & Public Health
Metastasis
Molecular Medicine
Molecular subtypes
Mutation
Oncology
Radiotherapy
Software
Surgical Oncology
BRAF V600E
Molecular subtypes
Immunotherapy
Colorectal cancer
Machine learning
IDO1
ISSN:2730-6011, 2730-6011
Online-Zugang:Volltext
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Zusammenfassung:Background Immunotherapy is an effective treatment for BRAF V600E-mutant colorectal cancer, but currently, only a few benefit from it. Therefore, exploring new immunotherapy strategies is essential. Methods We obtained RNA sequencing data and clinical information of colorectal cancer patients from the TCGA and GEO databases. The impact of the BRAF V600E mutation on tumor microenvironment characteristics, gene expression, and signaling pathways was evaluated using bioinformatics approaches. Weighted gene co-expression network analysis (WGCNA) were used to identify core genes associated with T cell dysfunction. Consensus clustering was applied for subtype construction. Least Absolute Shrinkage and Selection Operator (LASSO) and Random Forest (RF) algorithms were employed to filter potential immunotherapy targets. Results We found that BRAF V600E mutation has a complex impact on the immune profile of colorectal cancer. It increases immune cell infiltration and activates immune-related signaling pathways, yet it also severely restricts T cell function. We subsequently identified 39 core genes associated with T cell dysfunction and constructed subtypes of BRAF V600E colorectal cancer based on their expression profiles. Significant heterogeneity was observed between these subtypes in immune signaling pathway activity, immune infiltration patterns, immune phenotype scores, and mechanisms of resistance to immunotherapy. Ultimately, using machine learning algorithms and bioinformatics validation, we identified IDO1 as a potential immunotherapy targets for BRAF V600E-mutant colorectal cancer. Conclusion This study constructed novel T cell dysfunction molecular subtypes for BRAF V600E-mutant colorectal cancer and identified IDO1 as a potential immunotherapy target, providing a new strategy for immunotherapy.
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ISSN:2730-6011
2730-6011
DOI:10.1007/s12672-025-01930-8