膀胱癌尿液差异蛋白鉴定及生物信息分析
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摘要
目的对膀胱癌患者和正常对照尿液中的差异蛋白进行鉴定和生物信息分析。方法应用swiss-prot、ProtParam、Uniprot、Gene Ontology、KEGG等数据库对前期研究中筛选出的膀胱癌尿液差异蛋白分别从蛋白、基因、核酸水平进行基本理化性质、分子功能、参与生物进程、细胞组分、代谢途径等方面的综合分析。结果前期研究中筛选出的30个差异点鉴定出22个蛋白质,合并去重后共得到14个蛋白质,分别为:β_2微球蛋白;脂肪细胞型脂肪酸结合蛋白;凝溶胶蛋白;凝溶胶蛋白亚型1;肌红蛋白;纤维蛋白原α链;载脂蛋白A-I;前列腺素合成酶;AMBP蛋白;转甲状腺素蛋白;角蛋白1;角蛋白8;推测蛋白白蛋白;推测蛋白甘露聚糖结合凝集素丝氨酸蛋白酶2。其中KRT8、KRT1、FGA、APOA1、FABP4、ALB、GSN、B2M、MASP2、TTR 10个基因均具有蛋白结合的分子功能;PTGDS、ALB、TTR 3个基因均具有转运蛋白活性的分子功能;ALB、MB2个基因具有氧结合功能,ALB还具有抗氧化活性。筛选的差异蛋白中大部分具有相似的本体注解,APOA1参与了膀胱癌分子通路途径中的PPAR信号通路。结论 14个膀胱癌尿液差异蛋白具有各自不同的理化属性,其基因产物具有蛋白结合、转运蛋白活性、氧结合及抗氧化活性的分子功能;参与了转运和细胞骨架合成等生物进程。结合生物信息学分析和大量文献检索,为下一步的靶蛋白研究提供方向。
Objective To conduct the bioinformatic analysis of urinary differential expression proteins between bladder cancer patients and normal controls. Methods Using swiss-prot,ProtParam,Uniprot,Gene Ontology and KEGG databases,we analyzed the basic physicochemical properties,molecular function,biological process and metabolic pathways of the 14 proteins. Results From twenty-two proteins identified from our previous study, 14 proteins were obtained after de-equalization. The proteins were:Beta-2-microglobulin; Fatty acid binding protein,adipocyte; Gelsolin; Isoform of GSN; Isoform 2 of Fibrinogen alpha chain; Apolipoprotein A-1; Prostaglandin D2 synthase 21 kDa(brain); Protein AMBP; Transthyretin; Keratin,cytoskeletal 1; and Keratin,cytoskeletal 8. Among them,KRT8,KRT1,FGA,APOA1,FABP4,ALB,GSN,B2M,MASP2,and TTR all had protein binding functions. PTGDS, ALB, and TTR had molecular transporter activity functions. ALB and MB had oxygen binding functions,and ALB had antioxidant activity. Most of the proteins had similar gene ontology annotations. APOA1 was involved in the PPAR signaling pathway in the bladder cancer molecular pathways from KEGG. Conclusion The 14 bladder cancer urinary differential proteins have different physical and chemical properties. The gene products have the molecular functions of protein binding, transport protein activity,oxygen binding and antioxidant activity. They are involved in the biological process,such as transport and cytoskeleton organization. Based on the bioinformatic analysis and large number of literatures, we are able to provide the research direction for the target proteins.
Objective To conduct the bioinformatic analysis of urinary differential expression proteins between bladder cancer patients and normal controls. Methods Using swiss-prot,ProtParam,Uniprot,Gene Ontology and KEGG databases,we analyzed the basic physicochemical properties,molecular function,biological process and metabolic pathways of the 14 proteins. Results From twenty-two proteins identified from our previous study, 14 proteins were obtained after de-equalization. The proteins were:Beta-2-microglobulin; Fatty acid binding protein,adipocyte; Gelsolin; Isoform of GSN; Isoform 2 of Fibrinogen alpha chain; Apolipoprotein A-1; Prostaglandin D2 synthase 21 kDa(brain); Protein AMBP; Transthyretin; Keratin,cytoskeletal 1; and Keratin,cytoskeletal 8. Among them,KRT8,KRT1,FGA,APOA1,FABP4,ALB,GSN,B2M,MASP2,and TTR all had protein binding functions. PTGDS, ALB, and TTR had molecular transporter activity functions. ALB and MB had oxygen binding functions,and ALB had antioxidant activity. Most of the proteins had similar gene ontology annotations. APOA1 was involved in the PPAR signaling pathway in the bladder cancer molecular pathways from KEGG. Conclusion The 14 bladder cancer urinary differential proteins have different physical and chemical properties. The gene products have the molecular functions of protein binding, transport protein activity,oxygen binding and antioxidant activity. They are involved in the biological process,such as transport and cytoskeleton organization. Based on the bioinformatic analysis and large number of literatures, we are able to provide the research direction for the target proteins.
引文
[1]周慧,雷婷,张曼.醇类沉淀法提取尿液蛋白的优化策略[J].广东医学,2012,33(11):1534-1536.
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[6]CAI J,ZHAO X,LEI T,et al. Urinary thyroid hormone parameters test for evaluating the thyroid function during pregnancy[J]. Syst Biol Reprod Med,2014,60(3):171-176.
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[8]MARCHEWKA Z, SZYMAИSKA B, DEMBOWSKI J, et al. Low molecular weight proteins and enzymes in the urine of patients with bladder cancer-a pilot study[J]. Cent European J Urol, 2018,71(3):280-286.
[9]ZHANG L, ZHOU Y, WU Q, et al. Effective prediction of preeclampsia by measuring serum angiotensin II, urinary angiotensinogen and urinary transforming growth factorβ1[J]. ExpTher Med,2017,14(1):391-397.
[10]KUWAMURA M,YOSHIDA H,YAMATE J,et al. Urinary bladder rhabdomyosarcoma(sarcoma botryoides)in a young Newfoundland dog[J]. J Vet Med Sci, 1998,60(5):619-621.
[11]Terada T. Sarcomatoid carcinoma of the urinary bladder:a case report with immunohistochemical and molecular genetic analysis[J]. Med Oncol,2010,27(2):547-553.
[12]WARRICK J I,WALTER V,YAMASHITA H. FOXA1,GATA3 and PPARγcooperate to drive luminal subtype in bladder cancer:a molecular analysis of established human cell lines[J]. Sci Rep,2016,6:38531.
[2]雷婷,赵旭宏,张曼.正常人尿蛋白质组学研究[J].广东医学,2010,31(3):30-32.
[3]LEI T,ZHAO X,JIN S,et al. Discovery of potential bladder cancer biomarkers by comparative urine proteomics and analysis[J]. Clin Genitourin Cancer,2013,11(1):56-62.
[4]TABAS-MADRID D, NOGALES-CADENAS R, PASCUALMONTANO A. GeneCodis3:a non-redundant and modular enrichment analysis tool for functional genomics[J]. Nucleic Acids Res,2012,40(Web Server issue):W478-W483.
[5]CHU L,FU G, MENG Q,et al. Identification of urinary biomarkers for type 2 diabetes using bead-based proteomic approach[J].Diabetes Res Clin Pract,2013,101(2):187-193.
[6]CAI J,ZHAO X,LEI T,et al. Urinary thyroid hormone parameters test for evaluating the thyroid function during pregnancy[J]. Syst Biol Reprod Med,2014,60(3):171-176.
[7]ZHANG M,FU G,LEI T. Two Urinary Peptides Associated Closely With Type 2 Diabetes Mellitus[J]. PloS One, 2015, 10(4):e0122950.
[8]MARCHEWKA Z, SZYMAИSKA B, DEMBOWSKI J, et al. Low molecular weight proteins and enzymes in the urine of patients with bladder cancer-a pilot study[J]. Cent European J Urol, 2018,71(3):280-286.
[9]ZHANG L, ZHOU Y, WU Q, et al. Effective prediction of preeclampsia by measuring serum angiotensin II, urinary angiotensinogen and urinary transforming growth factorβ1[J]. ExpTher Med,2017,14(1):391-397.
[10]KUWAMURA M,YOSHIDA H,YAMATE J,et al. Urinary bladder rhabdomyosarcoma(sarcoma botryoides)in a young Newfoundland dog[J]. J Vet Med Sci, 1998,60(5):619-621.
[11]Terada T. Sarcomatoid carcinoma of the urinary bladder:a case report with immunohistochemical and molecular genetic analysis[J]. Med Oncol,2010,27(2):547-553.
[12]WARRICK J I,WALTER V,YAMASHITA H. FOXA1,GATA3 and PPARγcooperate to drive luminal subtype in bladder cancer:a molecular analysis of established human cell lines[J]. Sci Rep,2016,6:38531.