ArticleDiscover oncology2025
Integrated single-cell transcriptomics and Mendelian randomization identify neutrophil-associated biomarker genes in colorectal cancer.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancer (CRC) is a prevalent digestive malignancy imposing significant economic burdens worldwide. However, the role and underlying mechanisms of neutrophil infiltration in CRC remain unclear. We therefore integrated single-cell RNA sequencing (scRNA-seq), Mendelian randomization (MR), and colocalization (coloc) analyses to uncover key neutrophil-related genes in CRC.
methodsNeutrophil marker genes were identified from scRNA-seq data (GSE231559) retrieved from the Gene Expression Omnibus (GEO). Expression quantitative trait locus (eQTL) data were obtained from the eQTLGen Consortium. An independent cohort from the BioBank Japan (BBJ-a-107) was utilized to conduct two-sample MR analyses, establishing causal relationships between differential gene expression and CRC risk. Subsequently, immune infiltration analyses, pseudotime analyses, and Immunohistochemical validation were performed, focusing on key genes.
resultsA total of 628 neutrophil-related differentially expressed genes were identified. MR analyses revealed 8 genes significantly associated with CRC risk, among which colocalization analyses pinpointed PRDX1 and FTH1 as key causal genes. These genes demonstrated significant associations with immune cell infiltration and participated in distinct biological pathways corresponding to diverse immune infiltration statuses. Pseudotime analyses supported the relevance of these key genes in CRC progression. Immunohistochemical validation showed that the target proteins were consistently upregulated in CRC tissues compared to normal tissues, confirming our bioinformatics predictions.
conclusionOur study highlights PRDX1 and FTH1 as neutrophil-associated genes causally linked to CRC, offering promising targets for future immunotherapeutic strategies.
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