Li Xubin, Kang Chunbo
Gastrointestinal Rehabilitation Center, Beijing Rehabilitation Hospital Affiliated to Capital Medical University, Beijing, China.
Medicine (Baltimore). 2025 May 9;104(19):e42319. doi: 10.1097/MD.0000000000042319.
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.
结直肠癌肝转移一般是指结直肠癌细胞通过血液循环进入肝脏并在肝脏内形成新肿瘤的过程。复合蛋白2（CPLX2）和突触体相关蛋白25（SNAP25）在结直肠癌肝转移恢复过程中的作用尚不清楚。从由GPL21047和GPL11154生成的基因表达综合数据库中下载了用于结直肠癌肝转移的数据集GSE147602和GSE144259。进行了批次归一化、差异表达基因（DEG）筛选、加权基因共表达网络分析、蛋白质-蛋白质相互作用网络的构建与分析、功能富集分析和基因集富集分析。绘制了基因表达热图。进行了免疫浸润分析和比较毒理基因组学数据库分析。使用TargetScan筛选调控核心DEG的miRNA。通过实验验证，共鉴定出1215个DEG。根据基因本体分析，它们主要富集于细胞信号传导、G蛋白偶联受体信号通路、信号转导受体结合和细胞因子结合。京都基因与基因组百科全书分析结果表明，靶细胞主要富集于胆固醇代谢嗅觉转导。在metascape的富集项目中，基因本体富集条目包括循环调节、肌肉结构发育、循环系统中的血管过程和细胞外基质组织。加权基因共表达网络分析的软阈值功率设置为4。通过对5种不同算法鉴定出的核心基因进行交叉，获得了4个核心基因，如维恩图所示。基因表达热图显示，核心基因（CPLX2、SNAP25和巴松管蛋白）在原发性结直肠癌中表达下调，在结直肠癌肝转移中表达上调。比较毒理基因组学数据库分析表明，3个基因（CPLX2、SNAP25和巴松管蛋白）与腹痛、黄疸、化学和药物性肝损伤及坏死有关。CPLX2基因的相关miRNA为hsa-miR-1-3p、hsa-miR-206、hsa-miR-613；SNAP25基因的相关miRNA为hsa-miR-181d-5p、hsa-miR-181b-5p、hsa-miR-181c-5p。结果证实，CPLX2和SNAP25正向调节磷脂酰肌醇3激酶-AKT信号通路，促进结直肠癌肝转移的进展。CPLX2和SNAP25基因在结直肠癌肝转移中过表达，可能作为重要的分子靶点。
