胰腺癌肝转移核心基因的筛选与验证  

Screening and identification of hub gene involved in hepatic metastasis of carcinoma of pancreas

作　　者：黄坤 何运胜 李建波 赵攀[1] 肖春波 赵平武[1] HUANG Kun;HE Yunsheng;LI Jianbo;ZHAO Pan;XIAO Chunbo;ZHAO Pingwu(Department of General Surgery,Mianyang Hospital of Traditional Chinese Medicine,Mianyang,Sichuan 621000,China)

机构地区：[1]四川省绵阳市中医医院普通外科

出　　处：《中国普通外科杂志》2023年第3期390-399,共10页China Journal of General Surgery

基　　金：四川省绵阳市应用技术研究与开发基金资助项目(2019YFZJ004)。

摘　　要：背景与目的:胰腺癌是预后极差的恶性肿瘤,其5年生存率约为11.5%,有将近半数的患者在初诊时已出现远处转移,而肝转移则占到其中的37.0%~41.9%。探索新的胰腺癌肝转移的生物标志物可能有助于提高患者治疗的效果。因此,本研究通过生物信息学方法寻找在胰腺癌肝转移过程起关键作用的基因并验证。方法:下载GEO数据库中的胰腺导管腺癌(PDAC)高通量测序数据集GSE151580(该数据集中包含胰腺癌肝转移病灶组织样本和原发病灶组织样本),使用R语言“limma”包筛选出肝转移病灶组织样本和原发病灶组织样本间的差异表达基因。对差异表达基因进行GO和KEGG功能富集。利用STRING数据库构建蛋白质间的相关作用关系,使用Cytoscape对蛋白质相互作用网络进行可视化展示并利用CytoHubba插件根据MCC拓扑分析方法,挑选MCC分数最高的前10位基因,确定为候选的核心基因。利用TCGA、GEPIA、UALCAN和HPA数据库的验证对候选的核心基因加以验证。结果:总共纳入分析基因数为46512个,符合筛选条件的差异表达基因数为491个,其中上调162个,下调329个。挑选MCC分数最高的前10位基因后,通过候选基因经验证显示,APOB基因在肿瘤组织中高表达(P<0.05),其表达产物主要定位于细胞质和细胞膜,免疫组化中等强度阳性。APOB基因的突变与患者的M分期有关,表现为该基因突变组中,M1患者构成比更大(P=0.0221);而该基因的表达与患者的总生存(OS)率和无病生存(DFS)率均无明显关系(均P>0.05)。此外,APOA4基因表达产物也主要定位于细胞质和细胞膜,免疫组化染色呈中等强度阳性。APOA4基因的突变与患者的TNM分期有关,表现为突变组中,TNM分期更早(P=0.0183)。该基因低表达患者的DFS更高(HR=1.75,P=0.025),但与患者的OS无关(P>0.05)。结论:APOB基因可能与胰腺癌的肝转移相关,有望作为胰腺癌肝转移早期筛查的分子标志物。APOA4Background and Aims:Pancreatic cancer is a highly malignant tumor with a very poor prognosis,with a 5-year survival rate of about 11.5%.Nearly half of the patients have distant metastasis at the time of initial diagnosis,and liver metastasis accounts for 37%to 41.9%of them.Exploring new biomarkers for pancreatic cancer liver metastasis may help improve the treatment efficacy in patients.Therefore,this study was conducted to identify and validate key genes that play a critical role in the process of pancreatic cancer liver metastasis using bioinformatics approaches.Methods:The high-throughput sequencing dataset GSE151580 for pancreatic ductal adenocarcinoma(PDAC)was downloaded from the GEO database,which included tissue samples from pancreatic cancer liver metastases and primary lesions.The differentially expressed genes between liver metastasis tissue samples and primary lesion tissue samples were screened using the R language limma package.The GO and KEGG functional enrichment analyses were performed on the differentially expressed genes.The protein-protein interaction networks were constructed using the STRING database,which were then visualized using Cytoscape.The top 10 genes were selected using the CytoHubba plugin based on the MCC topology analysis method,which were considered as the candidate core genes.Finally,the candidate core genes were validated using TCGA,GEPIA,UALCAN,and HPA databases.Results:A total of 46512 genes were included in the analysis,with 491 differentially expressed genes meeting the screening criteria,of which 162 were up-regulated and 329 were down-regulated.After selecting the top 10 genes with the highest MCC scores,validation of the candidate genes showed that the APOB gene was highly expressed in tumor tissues(P<0.05),with its expression product mainly located in the cytoplasm and cell membrane,and showing moderate positive staining in immunohistochemistry.APOB gene mutations were related to patients'M stage,with a higher proportion of Ml patients in the mutation group(P-0.0221).Ho

关 键 词：胰腺肿瘤 肿瘤转移 预后 载脂蛋白A类 计算生物学 

分 类 号：R735.9[医药卫生—肿瘤]