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A Genetically Engineered Mouse Model of Sporadic Colorectal Cancer
Published on: July 6, 2017
Unveiling immunogenic cell death-related genes in colorectal cancer: an integrated study incorporating transcriptome
Yu Shao1,2, Zhenling Wang1,2, Jingyu Wu1,2
1The First School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu, China.
Abstract:
Immunogenic cell death (ICD), a type of cell death that activates the tumor-specific immune response and thus exerts anti-tumor effects, is an emerging target in tumor therapy, but research on ICD-related genes (ICDGs) in colorectal cancer (CRC) remains limited. This study aimed to identify the CRC-specific ICDGs and explore their potential roles. Through RNA sequencing for tissue samples from CRC patients and integration with The Cancer Genome Atlas (TCGA) data, we identified 33 differentially expressed ICDGs in CRC. We defined the ICD score based on these genes in single-cell data, where a high score indicated an immune-active microenvironment. Additionally, molecular subtypes identified in bulk RNA data showed distinct immune landscapes. The ICD-related signature constructed with machine learning effectively distinguished patients' prognosis. The summary data-based Mendelian randomization (SMR) and colocalization analysis prioritized CFLAR for its positive association with CRC risk. Molecular docking revealed its stable binding with chemotherapeutic drugs like irinotecan. Furthermore, experimental validation confirmed CFLAR overexpression in CRC samples, and its knockdown inhibited tumor cell proliferation. Overall, this study expands the understanding of the potential roles and mechanisms of ICDGs in CRC and highlights CFLAR as a promising target for CRC.
Insights
This study identifies 33 immunogenic cell death-related genes (ICDGs) in colorectal cancer (CRC), revealing CFLAR as a key gene. Overexpression of CFLAR is linked to CRC risk and progression, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Immunogenic cell death (ICD) is crucial for anti-tumor immunity.
- Research on ICD-related genes (ICDGs) in colorectal cancer (CRC) is limited.
- Understanding ICDGs can reveal new therapeutic strategies for CRC.
Purpose of the Study:
- To identify CRC-specific ICDGs.
- To explore the roles of these genes in the tumor microenvironment and prognosis.
- To identify potential therapeutic targets for CRC.
Main Methods:
- RNA sequencing of CRC tissues and TCGA data integration.
- Development of an ICD score using single-cell data.
- Machine learning for prognostic signature construction.
- Mendelian randomization and molecular docking for gene prioritization.
Main Results:
- Identified 33 differentially expressed ICDGs in CRC.
- High ICD score correlated with an immune-active microenvironment.
- Prognostic signature effectively distinguished patient outcomes.
- CFLAR was prioritized for its association with CRC risk and drug binding.
Conclusions:
- ICDGs play significant roles in CRC development and immune evasion.
- CFLAR is a promising therapeutic target for colorectal cancer.
- This study provides a foundation for developing novel ICD-based CRC therapies.
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