基于生物信息学分析喹啉酸磷酸核糖基转移酶在恶性黑色素瘤中的表达及潜在生物学功能

Analysis of the expression and potential biological function of quinolinate phosphoribosyltransferase in malignant melanoma based on bioinformatics

目的通过生物信息学方法分析喹啉酸磷酸核糖基转移酶(QPRT)在恶性黑色素瘤中的表达及潜在生物学功能。方法应用癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)检索恶性黑色素瘤患者的临床资料。应用基因表达谱互动分析(GEPIA)数据库对TCGA数据库中恶性黑色素瘤组织和正常皮肤组织中QPRT mRNA表达水平进行分析。应用UALCAN数据库对TCGA数据库中不同临床分期恶性黑色素瘤组织中QPRT mRNA的表达水平进行分析。应用GEPIA数据库分析不同QPRT mRNA表达情况恶性黑色素瘤患者的预后。应用人类蛋白质参考数据库(HPRD)分析正常皮肤组织、原发性黑色素瘤组织及转移性黑色素瘤组织中QPRT蛋白的表达情况。应用GeneMANIA数据库查找与QPRT相互作用的蛋白,将与QPRT相互作用的关键基因利用WebGestalt进行基因本体(GO)分析,了解其参与的细胞组分、生物过程、生物功能。结果恶性黑色素瘤组织中QPRT mRNA表达水平明显高于正常皮肤组织,差异有统计学意义(P﹤0.01)。Ⅰ、Ⅱ、Ⅲ和Ⅳ期恶性黑色素瘤患者的QPRT mRNA表达水平比较,差异无统计学意义(P﹥0.05)。QPRT低表达组患者的总生存情况和无病生存情况均优于QPRT高表达组,差异均有统计学意义(P﹤0.05)。免疫组化显示,正常皮肤组织中QPRT蛋白阴性表达,恶性黑色素瘤组织中QPRT蛋白呈强阳性表达。GeneMANIA数据库中筛选出20个与QPRT相互作用的蛋白,相关关键基因主要参与蛋白结合、离子结合、核酸结合及转运活性等。结论QPRT基因在恶性黑色素瘤中高表达,其高表达与恶性黑色素瘤患者的预后不良相关,可能成为筛查恶性黑色素瘤的标志物及治疗靶点。

Objective To analyze the expression and potential biological function of quinolinate phosphoribosyltransferase(QPRT)in malignant melanoma by bioinformatics method.Method Clinical data of patients with malignant melanoma were searched by using The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.The Gene Expression Profiling Interactive Analysis(GEPIA)database was used to analyze the QPRT mRNA expression levels in malignant melanoma tissues and normal skin tissues in the TCGA database.The UALCAN database was used to analyze the expression levels of QPRT mRNA in malignant melanoma tissues of different clinical stages in the TCGA database.The prognosis of malignant melanoma patients with different QPRT mRNA expression was analyzed by using the GEPIA database.The Human Protein Reference Database(HPRD)was used to analyze the expression of QPRT protein in normal skin tissue,primary melanoma tissue,and metastatic melanoma tissue.The GeneMANIA database was used to search for proteins interacting with QPRT,and the key genes interacting with QPRT were analyzed by WebGestalt and Gene Ontology(GO)analysis was performed to understand the cellular components,biological processes,and biological functions involved.Result The expression level of QPRT mRNA in malignant melanoma tissues was significantly higher than that in normal skin tissues,and the difference was statistically significant(P<0.01).There was no significant difference in the expression levels of QPRT mRNA in patients with malignant melanoma in stages I,II,III,and IV(P>0.05).The overall survival and disease-free survival of patients in the QPRT low-expression group were better than those in the QPRT high-expression group,and the differences were statistically significant(P<0.05).Immunohistochemistry showed that QPRT protein was negatively expressed in normal skin tissue,and QPRT protein was strongly positively expressed in malignant melanoma tissue.Twenty proteins interacting with QPRT were screened out from the GeneMANIA database,with key genes mainly involved in protein binding,ion binding,nucleic acid formation,and transport activitiy.Conclusion QPRT gene is up-regulation in malignant melanoma,and its high expression is associated with poor prognosis of malignant melanoma patients.This molecule may become a marker for screening malignant melanoma and a promising therapeutic target.