【摘要】 目的探讨B7同源物5(B7-H5)在结直肠癌患者组织中的表达、临床意义和生物学功能。方法收集手术切除的结直肠癌患者癌组织及癌旁组织的石蜡标本69例,通过免疫组织化学染色法观察B7-H5蛋白的表达情况,分析B7-H5表达与患者临床病理因素之间的关系。利用预测相互作用的GeneMANIA程序获得与B7-H5存在相互作用的蛋白并构建蛋白相互作用网络图。使用基因功能注释分析工具Metascape数据库对B7-H5及相互作用蛋白进行基因本体(GO)生物学功能和京都基因与基因组百科全书(KEGG)信号通路富集分析。结果结直肠癌患者癌组织中B7-H5表达水平显著高于癌旁组织;B7-H5表达水平与患者的性别、年龄、肿瘤部位无明显相关性;与肿瘤临床分期和淋巴结转移情况呈显著正相关。GeneMANIA数据库显示B7-H5与半乳糖凝集素9(LGALS9)、含双PH结构域ArfGTP酶激活蛋白2(ADAP2)、 Ras和Rab相互作用蛋白3(RIN3)、 1号染色体可读框162(C1orf162)、 Src酪氨酸激酶家族原癌基因FGR等20个蛋白相互作用。GO生物学功能富集显示B7-H5蛋白集参与跨膜受体蛋白酪氨酸激酶信号通路、胞吐调控作用、淋巴细胞活化负调控、过氧化物代谢过程、磷脂酰肌醇磷酸盐结合、肽链内切酶活性调控、天然免疫调控和酶激活物活性调节。KEGG信号通路富集分析显示B7-H5蛋白集参与磷酸酪氨酸相互作用结构域/蛋白酪氨酸磷酸酶1B(PID/PTP1B)通路、 PID/白细胞介素8/CXC趋化因子受体1(PID/IL-8/CXCR1)通路和破骨细胞分化等信号通路。结论结直肠癌组织中B7-H5表达增高且与淋巴结转移和临床分期相关。此外,B7-H5蛋白集涉及细胞代谢、天然免疫和肿瘤免疫逃逸等过程。更多还原

【Abstract】 Objective To explore the expression, clinical significance, and biological functions of B7-H5 in the tissues of patients with colorectal cancer(CRC). Methods In 69 pairs of paraffinized CRC specimens and paracancerous tissues we collected, the protein expression of B7-H5 was detected by immunohistochemical staining. Furthermore, the relationship between the B7-H5 expression and clinicopathological factors of the patients was analyzed. The GeneMANIA database was used to obtain the proteins interacting with B7-H5 and construct a protein interaction network diagram. Based on the Metascape database, the biological function and signaling pathway of the enrichment of B7-H5 and interacting proteins were analyzed by GO and KEGG pathway enrichment analysis. Results The expression level of B7-H5 was significantly higher in the CRC tissues than that in the paracancerous tissues. The B7-H5 expression had no significant correlation with the patients’ gender, age, tumor site, while it was positively correlated with the clinical stage and lymph node metastasis. GeneMANIA database showed that B7-H5 interacts with 20 proteins, such as galectin 9(LGALS9), ArfGTP with dual PH domains 2(ADAP2), Ras and Rab interactor 3(RIN3), chromosome 1 open reading frame 162(C1orf162), and FGRproto-oncogene, Src family tyrosine kinase(FGR). Besides, GO enrichment analysis indicated that the B7-H5-related protein set was involved in transmembrane receptor protein tyrosine kinase signaling pathway, regulated exocytosis, negative regulation of lymphocyte activation, superoxide metabolic process, phosphatidylinositol phosphate binding, regulation of endopeptidase activity, regulation of innate immune response, and enzyme activator activity. The KEGG signaling pathway enrichment analysis showed that the B7-H5-related protein set was involved in the signaling pathways such as PID/PTP1B pathway, PID/IL-8/CXCR1 pathway, and osteoclast differentiation. Conclusion The increased expression of B7-H5 in the tissues of patients with CRC is associated with lymph node metastasis and clinical stage. In addition, the B7-H5-related protein set is involved in the processes such as cell metabolism, innate immunity, and tumor immune escape.更多还原