生物信息学分析鉴定循环肿瘤细胞APOH基因作为结直肠癌肝转移核心基因的研究  

Identification of core gene APOH involved in circulating tumor cells for colorectal cancer liver metastasis by bioinformatics analysis

作　　者：郝文德 郭家豪 翟志伟[1] 韩加刚[1] 王振军[1] Hao Wende;Guo Jiahao;Zhai Zhiwei;Han Jiagang;Wang Zhenjun(Department of General Surgery,Beijing Chaoyang Hospital,Capital Medical University,Beijing 100020,China;Central Laboratory,Beijing Obstetrics and Gynecology Hospital,Capital Medical University,Beijing 100026,China)

机构地区：[1]首都医科大学附属北京朝阳医院普外科,北京100020 [2]首都医科大学附属北京妇产医院中心实验室,北京100026

出　　处：《中国医学前沿杂志（电子版）》2024年第1期36-44,共9页Chinese Journal of the Frontiers of Medical Science(Electronic Version)

摘　　要：目的 循环肿瘤细胞(circulating tumor cells,CTCs)是结直肠癌(colorectal cancer,CRC)肝转移的关键环节,目前对CTCs进行检测和再培养仍存在局限性,迫切需要新的标志物来提高CRC患者血液中CTCs的检出率。方法 经综合生物信息学分析获得由CTCs分泌的在CRC肝转移中起重要作用的血液蛋白,并通过蛋白质相互作用(protein-protein interaction,PPI)网络分析和外部高通量基因表达(gene expression omnibus,GEO)数据集对核心基因进行筛选和验证。结果 共鉴定出由CTCs分泌的在CRC肝转移中起重要作用的4个核心基因,其中载脂蛋白H (apolipoprotein H,APOH)最为重要,其在CTCs和肝转移灶中的表达水平显著高于CRC原发灶和其他转移部位,且在血液中CTCs的APOH表达水平显著高于白细胞。受试者操作特征曲线分析显示APOH对CRC肝转移具有较佳的诊断效能。基于APOH预测的EHT1864、Lisitinib和Oxaliplatin可能是CRC患者的潜在治疗药物。结论APOH是由CTCs分泌且在CRC肝转移中起重要作用的核心基因。Objective The circulating tumor cells(CTCs)are a key link of colorectal cancer(CRC)liver metastasis.However,there are still some limitations in the detection and reculture of isolated CTCs.Thus,novel markers are urgently needed to improve the detection of CTCs in blood from CRC patients.Methods The blood proteins secreted by CTCs that played an important role in liver metastasis of CRC were obtained through comprehensive bioinformatics analysis and the core genes were screened and validated by protein-protein interaction(PPI)network analysis and external gene expression omnibus(GEO)datasets.Results A total of four core genes secreted by CTCs that played an important role in CRC liver metastasis were identified,among which the apolipoprotein H(APOH) was the most important,and its expression was significantly higher in CTCs and liver metastases compared to primary colorectal tumors and other metastatic sites,and the CTCs also exhibited higher APOH expression levels than white blood cells in the blood.Receiver operating characteristic curve analysis showed that APOH had better diagnostic efficacy for CRC liver metastases.EHT1864,Lisitinib and Oxaliplatin were predicted as potential therapeutic drugs for CRC patients based on APOH.Conclusion APOH is a core gene secreted by CTCs and plays an important role in CRC liver metastasis.

关 键 词：结直肠癌 肝转移 循环肿瘤细胞 载脂蛋白H 生物信息学分析 

分 类 号：R735.34[医药卫生—肿瘤]