The role of CPLX2 and SNAP25 genes in the rehabilitation of colorectal cancer liver metastases: CPLX2, SNAP25 in colorectal cancer liver metastases

Colorectal cancer liver metastasis generally refers to the process where colorectal cancer cells enter the liver through the bloodstream and form new tumors within the liver. The roles of complexin 2 (CPLX2) and synaptosome-associated protein 25 (SNAP25) in the recovery from colorectal cancer liver metastasis are not yet clear. Data sets GSE147602 and GSE144259 for colorectal cancer liver metastasis were downloaded from the gene expression omnibus database generated from GPL21047 and GPL11154. Batch normalization, differentially expressed genes (DEGs) screening, weighted gene co-expression network analysis, construction and analysis of the protein-protein interaction network, functional enrichment analysis, and Gene Set Enrichment Analysis were conducted. Heatmaps of gene expression were plotted. Immune infiltration analysis and Comparative Toxicogenomics Database analysis were performed. TargetScan was used to screen for miRNAs regulating central DEGs. Through experimental verification, a total of 1215 DEGs were identified. According to gene ontology analysis, they were mainly enriched in cell signaling, G-protein-coupled receptor signaling pathway, signal transduction receptor binding, and cytokine binding. Kyoto Encyclopedia of Genes and Genomes analysis results showed that the target cells were mainly enriched in cholesterol metabolism olfactory transduction. In the enrichment projects of metascape, gene ontology enrichment items included regulation of circulation, muscle structure development, vascular process in the circulatory system, and extracellular matrix organization. The soft-thresholding power for weighted gene co-expression network analysis was set to 4. Four core genes were obtained by intersecting the central genes identified by 5 different algorithms, as shown in a Venn diagram. The heatmap of gene expression showed that the core genes (CPLX2, SNAP25, and Bassoon) were underexpressed in primary colorectal cancer and overexpressed in colorectal cancer liver metastasis. Comparative Toxicogenomics Database analysis showed that 3 genes (CPLX2, SNAP25, and Bassoon) were related to abdominal pain, jaundice, chemical and drug-induced liver injury, and necrosis. The related miRNAs for the CPLX2 gene were hsa-miR-1-3p, hsa-miR-206, hsa-miR-613; for the SNAP25 gene were hsa-miR-181d-5p, hsa-miR-181b-5p, hsa-miR-181c-5p. The results confirmed that CPLX2 and SNAP25 positively regulated the phosphatidylinositol 3 kinase-AKT signaling pathway and promoted the progression of liver metastasis of colorectal cancer. CPLX2 and SNAP25 genes are overexpressed in colorectal cancer liver metastasis and may serve as important molecular targets.