Immune molecule diagnostics in colorectal cancer: CCL2 and CXCL11

Traditional serrated adenomas (TSAs) and sessile serrated adenomas (SSAs) are known precursors to colorectal cancer (CRC), but differentiating between them morphologically can be challenging. This study developed an immune molecule-based model to distinguish TSA from SSA using RNA sequencing data from the GEO datasets (GSE117606, GSE45270, GSE117607). Gene expression profiling was conducted with the R package GEOquery, and immune cell infiltration was assessed using CIBERSORTx. Differential expression analysis of immune-related genes was performed with the "limma" package. Enrichment analysis of differentially expressed genes (DEGs) was conducted using "clusterProfiler" for Gene Ontology and kyoto encyclopedia of genes and genomes pathways, identifying protein-protein interaction networks to find core hub genes. Notable differences in immune cell infiltration were observed among SSA, TSA, CRC, and healthy tissues, involving various immune cell types. A total of 45 DEGs (34 upregulated, 11 downregulated) were identified, with CCL2 and CXCL11 emerging as key hub genes. Their diagnostic potential was validated through receiver operating characteristic analysis in GEO datasets and clinical samples, while immunohistochemistry revealed decreased expression of CCL2 and CXCL11 in SSA compared to TSA and normal tissues, indicating their role in SSA pathogenesis and potential as molecular diagnostic markers. The diagnostic value of CCL2 is superior to that of CXCL11, while the diagnostic value of CXCL11 requires further experimental verification.