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Genetically evaluating the causal role of peripheral immune cells in colorectal cancer: a two-sample Mendelian
Runze Huang1,2, Xin Jin1,2, Ziting Jiang1,2
1Department of Hepatic Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, People's Republic of China.
Background:
Investigating novel therapeutic strategies for colorectal cancer (CRC) is imperative. However, there is limited research on the use of drugs to target peripheral blood immune cells in this context. To address this gap, we performed a two-sample Mendelian randomization (MR) analysis to identify potential therapeutic targets for CRC.
Methods:
We applied two-sample MR to identify the causal relationship between peripheral blood immune cells and CRC. GWAS data were obtained from the IEU OPEN GWAS project. Based on the implications from the MR results, we conducted a comprehensive database search and genetic analysis to explore potential underlying mechanisms. We predicted miRNAs for each gene and employed extensive research for potential therapeutic applications.
Results:
We have identified causal associations between two peripheral immune cells and colorectal cancer. Activated & resting Treg %CD4 + cell was positively associated with the risks of CRC, while DN (CD4-CD8-) %leukocyte cell exhibited a protective role in tumor progression. NEK7 (NIMA related kinase 7) and LHX9 (LIM homeobox 9) expressed in Treg cells were positively associated with CRC risks and may play a vital role in carcinogenesis.
Conclusions:
This study identified causal relationship between peripheral immune cell and CRC. Treg and DN T cells were implicated to own promoting and inhibiting effects on CRC progression respectively. NEK7 and LHX9 in Treg cells were identified as potential biotarget for antitumor therapies.
Insights
Novel research reveals specific immune cells influence colorectal cancer (CRC) risk. Regulatory T cells (Tregs) may increase CRC risk, while DN T cells show a protective effect, offering new therapeutic targets.
Area of Science:
- Immunology
- Oncology
- Genetics
Background:
- Colorectal cancer (CRC) necessitates novel therapeutic strategies.
- Limited research exists on targeting peripheral blood immune cells for CRC treatment.
- A two-sample Mendelian randomization (MR) analysis was conducted to identify potential therapeutic targets for CRC.
Purpose of the Study:
- To investigate the causal relationship between peripheral blood immune cells and colorectal cancer (CRC).
- To identify potential therapeutic targets for CRC by analyzing immune cell associations.
- To explore underlying genetic mechanisms and potential therapeutic applications.
Main Methods:
- Two-sample Mendelian randomization (MR) analysis was applied.
- Genome-wide association study (GWAS) data were sourced from the IEU OPEN GWAS project.
- Database searches, genetic analysis, miRNA prediction, and literature review were performed.
Main Results:
- Causal associations were found between two peripheral immune cell types and CRC.
- Activated & resting regulatory T cells (Tregs) showed a positive association with CRC risk.
- DN (CD4-CD8-) cells demonstrated a protective role in CRC progression.
- NEK7 and LHX9 genes within Treg cells were positively associated with CRC risk and may be vital in carcinogenesis.
Conclusions:
- A causal relationship between peripheral immune cells and CRC was identified.
- Treg cells are implicated in promoting CRC progression, while DN T cells inhibit it.
- NEK7 and LHX9 in Treg cells represent potential therapeutic targets for CRC treatment.
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