Exploring the Application of Cathepsins in the Diagnosis and Treatment of Colorectal Cancer Based on Bioinformatics and Mendelian Randomization
GUO Dongqi
ZHANG Ping
WANG Yuan
ZHANG Jingru
BAI Jianqi
SU Hongmei
GUO Xiaofei
Abstract：Objective This study aims to explore the potential of cathepsins as diagnostic biomarkers and therapeutic targets for colorectal cancer using integrated bioinformatics and Mendelian randomization methods.Methods Transcriptomic data of colorectal cancer were obtained from the TCGA database for bioinformatics analysis to evaluate the expression levels of cathepsins in colorectal cancer and identify potential diagnostic biomarkers.GWAS data for nine cathepsins (cathepsins B,E,F,G,H,L2,O,S,and Z) were obtained from the IEU OpenGWAS project,and colorectal cancer GWAS data were sourced from the FinnGen consortium for Mendelian randomization analysis.This was done to assess the causal relationships between cathepsins and colorectal cancer and to evaluate their potential as drug targets.Results Cathepsins F,G,and O were found to be downregulated in colorectal cancer tumor tissues compared to adjacent normal tissues,whereas the other six cathepsins were upregulated (P<0.001).Excluding E and O,even cathepsins had an area under the ROC curve greater than 0.7,with cathepsins H and L2 having an area under the ROC curve greater than 0.9.The level of cathepsin H showed an inverse causal relationship with colorectal cancer (Inverse-Variance Weighted:OR=0.95,95％CI:0.92-0.99,P<0.01),while no causal relationships were found for other cathepsins with colorectal cancer (P>0.05).Conclusion Cathepsins H and L2 show good diagnostic efficacy for colorectal cancer and are potential diagnostic biomarkers.Higher concentrations of cathepsin H may reduce the risk of colorectal cancer,indicating its potential as a therapeutic target.
Keywords：CathepsinsColorectal cancerBioinformaticsMendelian randomization
Publication Date：2024-07-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 933-938 )