目的: 利用在线数据库和生物信息学的方法,研究BUB1B在胰腺腺癌(pancreatic adenocarcinoma,PAAD)组织中的表达水平及与预后和免疫细胞浸润的相关性。方法: 利用GEPIA数据库分析BUB1B在各种癌症中的表达情况;GEPIA、Kaplan-Meier Plotter数据库检索BUB1B的表达与PAAD患者预后的相关性;随后利用String数据库构建BUB1B共表达基因的蛋白互作网络,并用David数据库分析其GO生物学功能及KEGG信号通路;最后使用TIMER数据库分析BUB1B基因的表达与免疫浸润细胞之间的相关性。结果: 在PADD组织中,BUB1B表达水平高于正常组织(P<0.01);BUB1B的高转录水平与性别、年龄、种族、肥胖状况、饮酒习惯、慢性胰腺炎、淋巴转移和癌症阶段密切相关(P<0.05);BUB1B mRNA表达水平与PAAD预后和免疫细胞浸润相关(P<0.05) 。结论: BUB1B在PADD中高表达,与PAAD预后、免疫浸润相关,可作为胰腺癌诊断、预后、药物治疗的潜在标志物。
Objective: To study the expression level, prognosis and correlation with immune cell infiltration of BUB1B in pancreatic adenocarcinoma ( PAAD ) by online database and bioinformatics. Methods: The expression of BUB1B in various cancers was analyzed by GEPIA database. The correlation between the expression of BUB1B and the prognosis of PAAD patients was searched by GEPIA and Kaplan-Meier Plotter database. Then, the protein interaction network of BUB1B co-expressed genes was constructed by using String database, and its GO biological function and KEGG signaling pathway were analyzed by using David database. Finally, the TIMER database was used to analyze the correlation between the expression of BUB1B gene and immune cell infiltrating cells. Results: The expression level of BUB1B in PADD tissues was higher than that in normal tissues (P<0.01). The high transcription level of BUB1B was closely related to gender, age, race, obesity, drinking habits, chronic pancreatitis, lymph node metastasis and cancer stage (P<0.05). The expression level of BUB1B mRNA was associated with prognosis and immune cell infiltration (P<0.05). Conclusion: BUB1B is highly expressed in PADD, which is related to prognosis and immune infiltration, and can be used as a potential marker for diagnosis, prognosis and drug treatment of pancreatic cancer.
[1] Bray F, Ferlay J, Soerjomataram I, et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin, 2018, 68(6): 394-424.
[2] Balsano R, Tommasi C, Garajova I.State of the art for metastatic pancreatic cancer treatment: where are we now? [J].Anticancer Res, 2019,39(7):3405-3412.
[3] Huang JJ, Lok V, Ngai CH, et al.Worldwide burden of, risk factors for, and trends in pancreatic cancer[J].Gastroenterology, 2021,160(3):744-754.
[4] Kiyomitsu T, Obuse C, Yanagida M.Human Blinkin/AF15q14 is required for chromosome alignment and the mitotic checkpoint through direct Interaction with Bub1 and BubR1[J].Dev Cell, 2007,13(5):663-676.
[5] Zhu LJ, Pan Y, Chen XY, et al.Bub1 promotes proliferation of liver cancer cells byActivating SMAD2 phosphorylation[J].Oncol Lett, 2020,19(5):3506-3512.
[6] Grabsch H, Takeno S, Parsons WJ, et al.Overexpression of the mitotic checkpoint genes Bub1, Bubr1, and Bub3 in gastric cancer: association with tumour cell proliferation[J].J Pathol, 2003,200(1):16-22.
[7] Grabsch HI, Askham JM, Morrison EE, et al.Expression of Bub1 protein in gastric cancer correlates with the histological subtype, but not with DNA ploidy or microsatellite instability[J].J Pathol, 2004,202(2):208-214.
[8] Chen HL, Lee J, Kljavin NM, et al.Requirement for Bub1b/Bubr1 in tumor progression of lung adenocarcinoma[J].Genes Cancer, 2015,6:106-118.
[9] Song YJ, Tan J, Gao XH, et al.Integrated analysis reveals key genes with prognostic value in lung adenocarcinoma[J].Cancer Manage Res, 2018,10:6097-6108.
[10] Tang ZF, Li CW, Kang BX, et al.GEPIA: a Web server for cancer and normal gene expression profiling and interactive analyses[J].Nucleic Acids Res, 2017,45:W98-W102.
[11] Nagy á, Lanczky A, Menyhart O, et al.Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets[J].Sci Rep, 2018,8(1):9227.
[12] Li TW, Fu JX, Zeng ZX, et al.TIMER2.0 for analysis of tumor-infiltrating immune cells[J].Nucleic Acids Res, 2020,48:W509-W514.
[13] Borcoman E, Kamal M, Marret G, et al.HDAC inhibition to prime immune checkpoint inhibitors[J].Cancers, 2021,14(1):66.
[14] Yang S, Liu T, Nan HM, et al.Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of cutaneous melanoma[J].J Cell Physiol, 2020,235(2):1025-1035.