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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| Vydané v: | Discover. Oncology Ročník 16; číslo 1; s. 163 - 20 |
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| Hlavní autori: | , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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New York
Springer US
12.02.2025
Springer Nature B.V Springer |
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| Abstract | 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. |
|---|---|
| AbstractList | 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. 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.BACKGROUNDImmunotherapy 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.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.METHODSWe 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.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.RESULTSWe 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.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.CONCLUSIONThis 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. Abstract 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. BackgroundImmunotherapy 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.MethodsWe 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.ResultsWe 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.ConclusionThis 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. 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. 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. 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. 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. |
| Author | Qi, Haonan Hu, Hanqing Gu, Tiefeng Sun, Liangwei Wang, Jiaqi Su, Yongqi |
| Author_xml | – sequence: 1 givenname: Tiefeng surname: Gu fullname: Gu, Tiefeng organization: Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University – sequence: 2 givenname: Haonan surname: Qi fullname: Qi, Haonan organization: Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University – sequence: 3 givenname: Jiaqi surname: Wang fullname: Wang, Jiaqi organization: Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University – sequence: 4 givenname: Liangwei surname: Sun fullname: Sun, Liangwei organization: Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University – sequence: 5 givenname: Yongqi surname: Su fullname: Su, Yongqi organization: Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University – sequence: 6 givenname: Hanqing surname: Hu fullname: Hu, Hanqing email: huhanqing@hrbmu.edu.cn organization: Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/39934467$$D View this record in MEDLINE/PubMed |
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| Keywords | BRAF V600E Molecular subtypes Immunotherapy Colorectal cancer Machine learning IDO1 |
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| Snippet | Background
Immunotherapy is an effective treatment for BRAF V600E-mutant colorectal cancer, but currently, only a few benefit from it. Therefore, exploring new... Immunotherapy is an effective treatment for BRAF V600E-mutant colorectal cancer, but currently, only a few benefit from it. Therefore, exploring new... BackgroundImmunotherapy is an effective treatment for BRAF V600E-mutant colorectal cancer, but currently, only a few benefit from it. Therefore, exploring new... Abstract Background Immunotherapy is an effective treatment for BRAF V600E-mutant colorectal cancer, but currently, only a few benefit from it. Therefore,... |
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| SubjectTerms | 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 |
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| Title | Identification of T cell dysfunction molecular subtypes and exploration of potential immunotherapy targets in BRAF V600E-mutant colorectal cancer |
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