CXCL10 promotes non-small cell lung cancer (NSCLC) progression by modulating the phosphate to urate ratio (PUR)

This study aims to explore the causal relationships and mechanisms between NSCLC-related genes, metabolites, and NSCLC using Mendelian Randomization (MR). The study employed differential gene expression analysis, two-sample MR analysis, and mediation analysis, utilizing NSCLC Genome-Wide Association Study (GWAS) data from the Finngen database, gene data from the eQTLGen and pQTL databases, and NSCLC expression data from the Gene Expression Omnibus (GEO) database. First, two-sample MR analysis was performed to evaluate the causal relationships between expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) genes and NSCLC. Violin plots were then used to validate the expression levels of these genes in NSCLC. Finally, mediation analysis was conducted to explore the mediating role of metabolites in the relationship between gene expression and NSCLC development. Our study found a significant positive association between high expression of the CXCL10 gene and increased NSCLC risk. Further mediation analysis revealed that CXCL10 promotes NSCLC development by regulating the PUR. Specifically, the mediation effect was 0.039, with a mediation proportion of 25.4% and a P-value of 0.012. This study provides new insights into the molecular mechanisms of CXCL10 in NSCLC and suggests its potential as a biomarker for future targeted therapeutic strategies.