Li Xiaoyan, He Jie, Yu Mi, Zhang Wei, Sun Jian
Department of endocrinology, First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China.
Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2020 May 30;40(5):683-692. doi: 10.12122/j.issn.1673-4254.2020.05.11.
To investigate the expression of BUB1 gene in gastric cancer.
Oncomine, GEPIA, BioGPS and Kaplan-Meier Plotter databases were used to analyze the difference of BUB1 gene expression between gastric cancer tissue and normal gastric tissue. The association of BUB1 expression level with the prognosis of gastric cancer patients was also analyzed. The Cancer Cell Line Encyclopedia (CCLE) was explored to analyze the expression of BUB1 in T cells and B cells in gastric cancer patients, and the String database was used to generate the network map of BUB1-related proteins and functional annotation of gene ontology (GO). The related pathways of KEGG were analyzed. Tumor immune assessment resource (TIMER) database was used to analyze the expression of BUB1 in immune infiltration and its effect on prognosis of gastric cancer patients. To further verify the results of gene chip analysis in Oncomine database, we collected 30 pairs of surgical specimens of gastric adenocarcinoma and adjacent tissues from patients admitted to the First Affiliated Hospital of Chengdu Medical College from March, 2018 to July, 2019. The results of BUB1 gene expression in Oncomine database were verified by PCR and immunohistochemistry.
Oncomine, GEPIA and BioGPS analyses showed that BUB1 was highly expressed in gastric cancer compared with normal gastric tissue. Kaplan-Meier survival analysis showed that the progression-free survival time (HR=0.52, 95% :0.41-0.67, < 0.05) and the overall survival time (HR=0.67, 95% :0.55-0.82, < 0.05) were prolonged in gastric cancer patients with a high expression of BUB1. Through String data collection, BUB1-related proteins were mainly enriched in 13 cellular components, 4 molecular functions and 12 biological processes, involving 4 signal pathways. TIMER database analysis showed that CD4 T cells and macrophages with high expressions of BUB1 mRNA in the immune microenvironment were associated with a favorable 5-year survival outcome of patients with gastric cancer. In the surgical specimens, real-time quantitative PCR showed that the expression level of BUB1 mRNA was significantly higher in gastric cancer tissues than in the adjacent gastric mucosa tissues, and immunohistochemical results demonstrated positive BUB1 staining in the gastric cancer tissues.
BUB1 gene is highly expressed in gastric cancer. BUB1 may reduce tumor immunosuppression and helps to evaluate the prognosis of patients with gastric cancer.
探讨BUB1基因在胃癌中的表达情况。
利用Oncomine、GEPIA、BioGPS和Kaplan-Meier Plotter数据库分析胃癌组织与正常胃组织中BUB1基因表达的差异。同时分析BUB1表达水平与胃癌患者预后的相关性。通过癌症细胞系百科全书（CCLE）分析胃癌患者T细胞和B细胞中BUB1的表达情况，并利用String数据库生成BUB1相关蛋白的网络图及基因本体论（GO）功能注释，分析KEGG相关通路。利用肿瘤免疫评估资源（TIMER）数据库分析BUB1在免疫浸润中的表达及其对胃癌患者预后的影响。为进一步验证Oncomine数据库中基因芯片分析的结果，我们收集了成都医学院第一附属医院2018年3月至2019年7月收治患者的30对胃腺癌手术标本及癌旁组织，通过PCR和免疫组化验证Oncomine数据库中BUB1基因表达的结果。
Oncomine、GEPIA和BioGPS分析显示，与正常胃组织相比，BUB1在胃癌中高表达。Kaplan-Meier生存分析显示，BUB1高表达的胃癌患者无进展生存期（HR=０.52，95%：0.41-0.67，＜0.05）和总生存期（HR=0.67，95%：0.55-0.82，＜0.05）延长。通过String数据收集，BUB1相关蛋白主要富集于13个细胞成分、4个分子功能和12个生物学过程，涉及4条信号通路。TIMER数据库分析显示，免疫微环境中BUB1 mRNA高表达的CD4 T细胞和巨噬细胞与胃癌患者良好的5年生存结局相关。在手术标本中，实时定量PCR显示胃癌组织中BUBmRNA的表达水平显著高于癌旁胃黏膜组织，免疫组化结果显示胃癌组织中BUB1染色呈阳性。
BUB1基因在胃癌中高表达。BUB1可能降低肿瘤免疫抑制作用，有助于评估胃癌患者的预后。
