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.

PubMed
Abstract

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.