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Published on: July 3, 2013
Exploring the pathogenic mechanism of RNH1 in colorectal cancer based on eQTL, Multi-omics and deep learning
Changan Chen1, Xintian Chen1, Yuping Yang1
1Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China.
Background:
Colorectal cancer (CRC) is a major global health concern with increasing incidence. Current treatments, though improved, require novel biomarkers for better diagnosis and management. Disulfidptosis, a recently characterized form of cell death, may play a critical role in CRC progression.
Methods:
Utilizing summary-data-based Mendelian randomization (SMR), we identified RNH1 as a gene linked to CRC and disulfidptosis. The expression and intercellular communication of RNH1 in CRC were analyzed using single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing (stRNA-seq). A prognostic model was built using a Deep Learning Survival Neural Network (DeepSurv). Additionally, we performed RNA sequencing (RNA-seq) analysis to analyze the function of RNH1. Validation was performed through qPCR on CRC and normal tissue samples.
Results:
RNH1 was identified as a gene linked to disulfidptosis and positively correlated with CRC risk. scRNA-seq analysis revealed that RNH1 + malignant cells showed distinct metabolic pathways and greater cell interactions. stRNA-seq analysis confirmed these interactions, especially with endothelial cells. DeepSurv analysis produced a prognostic model, showing different survival outcomes between high-risk and low-risk groups. RNA-seq analysis showed that the RNH1 + high expression group had higher immune cell abundance scores and tumor microenvironment scores, and RNH1 was positively correlated with most immune checkpoints. Drug sensitivity analysis suggested that CRC patients with high RNH1 expression were more sensitive to certain therapeutic agents. qPCR showed that the expression level of RNH1 in cancer tissues of CRC patients was significantly higher than that in normal tissues.
Conclusion:
RNH1 acts as a biomarker for CRC, influencing tumor growth via disulfidptosis, tumor microenvironment alterations, and metabolic pathways. Its high expression correlates with immune escape. This study suggests RNH1 as a potential therapeutic target for CRC, warranting further exploration of its mechanistic roles and treatment potential.
Insights
RNH1 is identified as a key gene in colorectal cancer (CRC) progression, influencing tumor growth through disulfidptosis and altering the tumor microenvironment. High RNH1 expression indicates potential as a therapeutic target for CRC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancer (CRC) presents a growing global health challenge.
- Novel biomarkers are crucial for improved CRC diagnosis and management.
- Disulfidptosis, a cell death mechanism, may significantly impact CRC development.
Purpose of the Study:
- To investigate the role of the RNH1 gene in colorectal cancer.
- To explore RNH1's connection with disulfidptosis and CRC risk.
- To evaluate RNH1 as a potential prognostic biomarker and therapeutic target in CRC.
Main Methods:
- Summary-data-based Mendelian randomization (SMR) to identify RNH1's link to CRC and disulfidptosis.
- Single-cell and spatial transcriptome sequencing (scRNA-seq, stRNA-seq) to analyze RNH1 expression and interactions.
- Deep Learning Survival Neural Network (DeepSurv) for prognostic model development.
- RNA sequencing (RNA-seq) and quantitative PCR (qPCR) for functional and expression analysis.
Main Results:
- RNH1 was identified as a gene positively correlated with CRC risk and disulfidptosis.
- RNH1+ malignant cells exhibit distinct metabolic pathways and enhanced intercellular communication, particularly with endothelial cells.
- A DeepSurv prognostic model differentiated survival outcomes; high RNH1 expression correlated with increased immune cell abundance, altered tumor microenvironment, and sensitivity to certain therapies.
- qPCR confirmed significantly higher RNH1 expression in CRC tissues compared to normal tissues.
Conclusions:
- RNH1 serves as a biomarker for CRC, impacting tumor growth via disulfidptosis, metabolic pathways, and the tumor microenvironment.
- Elevated RNH1 expression is linked to immune escape mechanisms in CRC.
- RNH1 represents a promising therapeutic target for colorectal cancer, meriting further investigation into its mechanisms and treatment potential.

