探索结直肠癌血清外泌体有效分子标志物  

Explore effective molecular markers of serum exosomes in colorectal cancer

作　　者：杨钊[1] 邹鲁飞 YANG Zhao;ZOU Lu-fei(Department of General Abdominal Surgery,The First People’s Hospital of Chenzhou,Chenzhou 423000,Hunan,China)

机构地区：[1]郴州市第一人民医院普通腹部外科,湖南郴州423000

出　　处：《生物医学工程与临床》2023年第6期785-795,共11页Biomedical Engineering and Clinical Medicine

摘　　要：目的基于血清外泌体数据结合加权基因共表达算法(WGCNA)和蛋白-蛋白互作分析(PPI)筛选结直肠癌(CRC)患者有效血清标志物,为预测CRC的发生提供帮助。方法从外泌体数据库(http://www.exorbase.org/)中下载健康人群和CRC患者血清外泌体基因表达数据,采用WGCNA和PPI对由118例健康人群和35例CRC患者组成的数据集进行分析,并利用外部的癌症基因组图谱(TCGA)数据库、GEO(https://www.ncbi.nlm.nih.gov/geo/)数据库中GSE192667和GSE24549数据集、R2预后平台(https://hgserver1.amc.nl/cgi-bin/r2/main.cgi)、CancerSEA(http://biocc.hrbmu.edu.cn/CancerSEA/)单细胞数据集和TIMER(https://cistrome.shinyapps.io/timer/)网站分析和验证核心分子。结果外泌体数据库中CRC患者较健康人群上调基因有5078个,下调基因有13004个。基于WGCNA和PPI算法获得了甘油醛3-磷酸脱氢酶基因(GAPDH)和微管蛋白α-1B基因(TUBA1B)作为核心分子。并通过内部数据集验证GAPDH和TUBA1B表达与CRC发生相关,可以作为有效的血清外泌体分子标志物。同时,外部TCGA数据集中上述两个基因在肿瘤组织中均高表达,在R2生存平台中高表达GAPDH和TUBA1B患者预后更差。同时在GSE192667和GSE24549数据集也获得了相似的结果。基于GSE192667数据集构建并验证了生存风险模型[生存风险模型得分=GAPDH表达量×0.0015+TUBA1B表达量×(-0.0002)]。利用CancerSEA网站和TIMER网站并结合基因集富集分析(GSEA)发现核心分子涉及了多个肿瘤相关通路和功能。结论利用血清外泌体数据库结合WGCNA和PPI算法,筛选获得的GAPDH和TUBA1B可以作为CRC患者有效的血清外泌体分子标志物。Objective To screen out effective molecular markers in colorectal cancer(CRC)patients based on serum exosome data by using the weighted gene co-expression network analysis and protein-protein interact(PPI),and help predict the occurrence of CRC.Methods Gene expression data of healthy people and CRC were downloaded from serum exosome database(http://www.exorbase.org/),the WGCNA and PPI were used to analyze the data set with 118 healthy and 35 CRC patients.The core molecules were analyzed and verified by using The Cancer Genome Atlas(TCGA)database,GSE192667 and GSE24549 data sets in GEO(https://www.ncbi.nlm.nih.gov/geo/)database,R2 prognostic platform(https://hgserver1.amc.nl/cgibin/r2/main.cgi),Cancer-SEA(http://biocc.hrbmu.edu.cn/CancerSEA/)single cell data set and TIMER(https://cistrome.shinyapps.io/timer/)website.Results Compared with healthy,in exosome database,there were 5078 up-regulated genes and 13004 down-regulated genes in CRC patients.Based on WGCNA and PPI algorithms,glyceraldehyde 3-phosphate dehydrogenase gene(GAPDH)and tubulinα-1b gene(TUBA1B)were obtained as core molecules.The expressions of GAPDH and TUBA1B were verified by internal data sets to be related to the occurrence of CRC and were effective serum exosome molecular markers.In external TCGA data set,those 2 genes were highly expressed in tumor tissues,and patients with high expression of GAPDH and TUBA1B in R2 platform showed worse prognosis,and the similar results were obtained on GSE192667 and GSE24549 datasets.The survival analysis model was constructed and verified based on GSE192667 data set[survival risk model score=GAPDH expression×0.0015+TUBA1B expression×(-0.0002).The CancerSEA website and TIMER website combined with gene set enrichment analysis(GSEA)found that core molecules were involved in multiple tumor-related pathways and functions.Conclusion It is demonstrated that using serum exosome database combined with WGCNA and PPI,the GAPDH and TUBA1B can be used as an effective serum exosome biomarkers in CRC patients.

关 键 词：结直肠癌 血清外泌体 基因加权共表达算法(WGCNA) 甘油醛3-磷酸脱氢酶基因(GAPDH) 微管蛋白α-1B基因(TUBA1B) 

分 类 号：R735.34[医药卫生—肿瘤]