
FOLLOWUS
1College of Biological and Pharmaceutical Engineering, West Anhui University, Lu’an 237012, Anhui, China
2Anhui Engineering Laboratory for Conservation and Sustainable Utilization of Traditional Chinese Medicine Resources, Lu’an 237012, Anhui, China
*Tel: 86-13516482068, E-mail: 646923623@qq.com
收稿日期:2020-08-02,
网络出版日期:2020-12-25,
纸质出版日期:2021-06-30
Scan QR Code
蒋平, 孙桃桃, 陈存武, 等. 基于生物信息学分析肾透明细胞癌预后相关关键基因[J]. 中国医学科学杂志(英文版), 2021,36(2):127-134.
Jiang Ping, Sun Taotao, Chen Cunwu, et al. Identification of Prognostic Related Hub Genes in Clear-Cell Renal Cell Carcinoma
蒋平, 孙桃桃, 陈存武, 等. 基于生物信息学分析肾透明细胞癌预后相关关键基因[J]. 中国医学科学杂志(英文版), 2021,36(2):127-134. DOI: 10.24920/003651.
Jiang Ping, Sun Taotao, Chen Cunwu, et al. Identification of Prognostic Related Hub Genes in Clear-Cell Renal Cell Carcinoma
目的
识别与肾透明细胞癌预后相关的关键基因。
方法
基于生物信息学分析技术对GEO数据库中的62个肾透明细胞癌样本和54个正常肾组织的数据集(GSE12606
GSE36895和GSE66272)进行分析。首先在GEO2R和J Venn网站上获取差异表达基因基因
之后采用GO和KEGG对基因进行功能注释;在使用STRING网站构建PPI网络后
采用Cytoscape软件的MCODE App对核心基因进行筛选;最后利用GEPIA网站分析与生存率有关的核心基因。
结果
我们共发现648个差异表达基因
包括222个上调表达基因和426个下调表达基因。PPI蛋白网络分析共发现28个表达上调的核心基因
其中7个核心基因(
CCNE2
CDK1
CDC6
CCNB2
BUB1
TTK
和
PTTG1
)富集于细胞周期
4个(
CCNE2
CDK1
CCNB2
和
RRM2
)富集于p53信号通路。GEPIA生存率分析发现:
CDK1
CCNB2
RRM2
BUB1
PTTG1
与肾透明细胞癌患者的生存率密切相关。肾透明细胞癌患者
BUB1
CCNB2
PTTG1
和
RRM2
等4个关键基因的表达量高于正常人群(
P
<
0.05)。
结论
BUB1
、
CCNB2
、
PTTG1
、
RRM2
等4个上调差异表达基因可能是肾透明细胞癌患者预后关键预测基因。
Objective
To identify new genes that correlate with prognosis of clear-cell renal cell carcinoma (ccRCC)
via
bioinformatics analysis.
Methods
The gene expression profiles of 62 ccRCC and 54 normal kidney tissues were available from the Gene Expression Omnibus database: GSE12606
GSE36895 and GSE66272. The differentially expressed genes were screened with GEO2R and J Venn online tools. Functional annotation including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was applied to identify the possible function of the hub genes involved in prognosis of ccRCC. In protein protein interaction network (PPI network)
the STRING online tool was used to visualize the network of the differentially expressed genes
and the core gene was selected by MCODE App in Cytoscape software. Finally
GEPIA Survival Plot was performed to assess genes associated with worse survival.
Results
We totally found 648 differentially expressed genes
including 222 up-regulated genes and 426 down-regulated genes. PPI network showed that in 28 up-regulated genes 7 (
CCNE2
CDK1
CDC6
CCNB2
BUB1
TTK
and
PTTG1
) enriched in cell cycle and 4 genes (
CCNE2
CDK1
CCNB2
and
RRM2
) enriched in p53 signaling pathway. GEPIA Survival Plot assay revealed that ccRCC patients carrying
CDK1
CCNB2
RRM2
BUB1
and
PTTG1
had a worse survival. GEPIA Box Plot showed that
BUB1
CCNB2
PTTG1
and
RRM2
were over expressed in the ccRCC tissues in contrast to the normal tissues (
P
<
0.05).
Conclusion
ccRCC patients with the four up-regulated differentially expressed genes including
BUB1
CCNB2
PTTG1
and
RRM2
might manifest a poor prognosis.
Li P , Znaor A , Holcatova I , et al . Regional geographic variations in kidney cancer incidence tates in European countries . Eur Urol 2015 ; 67 ( 6 ): 1134 - 41 . doi: 10.1016/j.eururo.2014.11.001 1001-9294-36-2-127/j.eururo.2014.11.001 . DOI: 10.1016/j.eururo.2014.11.001 http://doi.org/10.1016/j.eururo.2014.11.001 https://linkinghub.elsevier.com/retrieve/pii/S0302283814011750 https://linkinghub.elsevier.com/retrieve/pii/S0302283814011750
Srinivasan R , Ricketts CJ , Sourbier C , et al . New strategies in renal cell carcinoma: targeting the genetic and metabolic basis of disease . Clin Cancer Res 2015 ; 21 ( 1 ): 10 - 7 . doi: 10.1158/1078-0432.CCR-13-2993 1001-9294-36-2-127/1078-0432.CCR-13-2993 . DOI: 10.1158/1078-0432.CCR-13-2993 http://doi.org/10.1158/1078-0432.CCR-13-2993 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-13-2993 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-13-2993
Siegel R , Naishadham D and Jemal A . Cancer statistics . CA Cancer J Clin 2013 ; 63 ( 1 ): 11 - 30 . doi: 10.3322/caac.21166 1001-9294-36-2-127/caac.21166 . DOI: 10.3322/caac.21166 http://doi.org/10.3322/caac.21166 http://doi.wiley.com/10.3322/caac.v63.1 http://doi.wiley.com/10.3322/caac.v63.1
Capitanio U and Montorsi F . Renal cancer . Lancet 2016 ; 387 ( 10021 ): 894 - 906 . doi: 10.1016/S0140-6736(15)00046-X 1001-9294-36-2-127/S0140-6736(15)00046-X . DOI: 10.1016/S0140-6736(15)00046-X http://doi.org/10.1016/S0140-6736(15)00046-X
Vogelstein B , Papadopoulos N , Velculescu VE , et al . Cancer genome landscapes . Science 2013 ; 339 ( 6127 ): 1546 - 58 . doi: 10.1126/science.1235122 1001-9294-36-2-127/science.1235122 . DOI: 10.1126/science.1235122 http://doi.org/10.1126/science.1235122 https://www.sciencemag.org/lookup/doi/10.1126/science.1235122 https://www.sciencemag.org/lookup/doi/10.1126/science.1235122
Feng H , Gu ZY , Li Q , et al . Identification of significant genes with poor prognosis in ovarian cancer via bioinformatical analysis . J Ovarian Res 2019 ; 12 ( 1 ): 35 . doi: 10.1186/s13048-019-0508-2 1001-9294-36-2-127/s13048-019-0508-2 . DOI: 10.1186/s13048-019-0508-2 http://doi.org/10.1186/s13048-019-0508-2
Na YQ , Ye ZQ , Sun YH , et al. Diagnosis and treatment of renal cell carcinoma guide manual . In: Xiao J, Yand F, editors. The Chinese department of urology disease diagnosis and treatment guide manual, 2014 ed. Beijing: People Health Publishing House , 2013 . p. 1 - 29 .
Li DY , Song YS . Comparison of clinical data of renal cell carcinoma between elderly and middle aged and young patients . J Modem Oncology 2017 ; 25 ( 5 ): 740 - 3 . doi: 10.3969/j. issn.1672-4992.2017.05.018 1001-9294-36-2-127/j. issn.1672-4992.2017.05.018 . DOI: 10.3969/j. issn.1672-4992.2017.05.018 http://doi.org/10.3969/j. issn.1672-4992.2017.05.018
Linehan WM , Walther MM , Zbar B . The genetic basis of cancer of the kidney . J Urol 2003 ; 170 ( 6 pt 1 ): 2163 - 72 . doi: 10.1097/01.ju.0000096060.92 397.ed 1001-9294-36-2-127/01.ju.0000096060.92 397.ed . DOI: 10.1097/01.ju.0000096060.92 397.ed http://doi.org/10.1097/01.ju.0000096060.92 397.ed http://www.jurology.com/doi/10.1097/01.ju.0000096060.92397.ed http://www.jurology.com/doi/10.1097/01.ju.0000096060.92397.ed
Duensing S , Hohenfellner M . Adjuvant therapy for renal cell carcinoma: settled for now . Lancet 2016 ; 387 ( 10032 ): 1973 - 4 . doi: 10.1016/S0140-6736(16)00653-X 1001-9294-36-2-127/S0140-6736(16)00653-X . DOI: 10.1016/S0140-6736(16)00653-X http://doi.org/10.1016/S0140-6736(16)00653-X
Krabbe LM , Bagrodia A , Margnlis V , et al . Surgical management of renal cell carcinoma . Semin Intervent Radiol 2014 ; 31 ( 1 ): 27 - 32 . doi: 10.1055/s-0033-1363840 1001-9294-36-2-127/s-0033-1363840 . DOI: 10.1055/s-0033-1363840 http://doi.org/10.1055/s-0033-1363840 http://www.thieme-connect.de/ejournals/journal/10.1055/s-00000068 http://www.thieme-connect.de/ejournals/journal/10.1055/s-00000068
Kim HS , Park KH , Sun AK , et al . Frequent mutations of human Mad2, but not Bub1, in gastric cancers cause defective mitotic spindle checkpoint . Mutat Res 2005 ; 578 ( 1-2 ): 187 - 201 . doi: 10.1016/j. mrfmmm.2005.05.020 1001-9294-36-2-127/j. mrfmmm.2005.05.020 . DOI: 10.1016/j. mrfmmm.2005.05.020 http://doi.org/10.1016/j. mrfmmm.2005.05.020 https://linkinghub.elsevier.com/retrieve/pii/S0027510705003635 https://linkinghub.elsevier.com/retrieve/pii/S0027510705003635
Mur P , De Voer RM , Olivera-Salguero R , et al . Germline mutations in the spindle assembly checkpoint genes BUB1 and BUB3 are infrequent in familial colorectal cancer and polyposis . Mol Cancer 2018 ; 17 ( 1 ): 23 . doi: 10.1186/s12943-018-0762-8 1001-9294-36-2-127/s12943-018-0762-8 . DOI: 10.1186/s12943-018-0762-8 http://doi.org/10.1186/s12943-018-0762-8 https://doi.org/10.1186/s12943-018-0762-8 https://doi.org/10.1186/s12943-018-0762-8
Myrie KA , Percy MJ , Azim JN , et al . Mutation and expression analysis of human BUB1 and BUB1B in aneuploid breast cancer cell lines . Cancer Lett 2000 ; 152 ( 2 ): 193 - 9 . doi: 10.1016/s0304-3835(00)00340-2 1001-9294-36-2-127/s0304-3835(00)00340-2 . DOI: 10.1016/s0304-3835(00)00340-2 http://doi.org/10.1016/s0304-3835(00)00340-2
Burum-Auensen E , Deangelis PM , Schjølberg AR , et al . Spindle proteins Aurora A and BUB1B, but not Mad2, are aberrantly expressed in dysplastic mucosa of patients with longstanding ulcerative colitis . J Clin Pathol 2017 ; 60 ( 12 ): 1403 - 8 . doi: 10.1136/jcp.2006.044305 1001-9294-36-2-127/jcp.2006.044305 . DOI: 10.1136/jcp.2006.044305 http://doi.org/10.1136/jcp.2006.044305 http://jcp.bmj.com/cgi/doi/10.1136/jcp.2006.044305 http://jcp.bmj.com/cgi/doi/10.1136/jcp.2006.044305
Moustakas A . The mitotic checkpoint protein kinase BUB1 is an engine in the TGF-β signaling apparatus . Sci Signal 2015 ; 8 ( 359 ):fs1. doi: 10.1126/scisignal.aaa4636 1001-9294-36-2-127/scisignal.aaa4636 . DOI: 10.1126/scisignal.aaa4636 http://doi.org/10.1126/scisignal.aaa4636
Nyati S , Schinske-sebolt K , Pitchiaya S , et al . The kinase activity of the Ser/Thr kinase BUB1 promotes TGF-β signaling . Sci Signal 2015 ; 8 ( 358 ):ra1. doi: 10.1126/scisignal.2005379 1001-9294-36-2-127/scisignal.2005379 . DOI: 10.1126/scisignal.2005379 http://doi.org/10.1126/scisignal.2005379
Qian XT , Song XK , He Y , et al . CCNB2 overexpression is a poor prognostic biomarker in Chinese NSCLC patients . Biomed Pharmacother 2015 ; 74 : 222 - 7 . doi: 10.1016/j.biopha.2015.08.004 1001-9294-36-2-127/j.biopha.2015.08.004 . DOI: 10.1016/j.biopha.2015.08.004 http://doi.org/10.1016/j.biopha.2015.08.004 https://linkinghub.elsevier.com/retrieve/pii/S0753332215001894 https://linkinghub.elsevier.com/retrieve/pii/S0753332215001894
Vermeulen K , Bockstaele DRV , Berneman ZN . The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer . Cell Prolif 2003 ; 36 ( 3 ): 131 - 49 . doi: 10.1046/j.1365-2184.2003.00266.x 1001-9294-36-2-127/j.1365-2184.2003.00266.x . DOI: 10.1046/j.1365-2184.2003.00266.x http://doi.org/10.1046/j.1365-2184.2003.00266.x http://doi.wiley.com/10.1046/j.1365-2184.2003.00266.x http://doi.wiley.com/10.1046/j.1365-2184.2003.00266.x
Park SH , Yu GR , Kim WH , et al . NF-Y-dependent cyclin B2 expression in colorectal adenocarcinoma . Clin Cancer Res 2007 ; 13 ( 3 ): 858 - 67 . doi: 10.1158/1078-0432.CCR-06-1461 1001-9294-36-2-127/1078-0432.CCR-06-1461 . DOI: 10.1158/1078-0432.CCR-06-1461 http://doi.org/10.1158/1078-0432.CCR-06-1461 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-06-1461 http://clincancerres.aacrjournals.org/lookup/doi/10.1158/1078-0432.CCR-06-1461
Wang DG , Chen G , Wen XY , et al . Identification of biomarkers for diagnosis of gastric cancer by bioinformatics . Asian Pac J Cancer Prev 2015 ; 16 ( 4 ): 1361 - 5 . doi: 10.7314/apjcp.2015.16.4.1361 1001-9294-36-2-127/apjcp.2015.16.4.1361 . DOI: 10.7314/apjcp.2015.16.4.1361 http://doi.org/10.7314/apjcp.2015.16.4.1361 http://koreascience.or.kr/journal/view.jsp?kj=POCPA9&py=2015&vnc=v16n4&sp=1361 http://koreascience.or.kr/journal/view.jsp?kj=POCPA9&py=2015&vnc=v16n4&sp=1361
Mo ML , Chen Z , Li J , et al . Use of serum circulating Ccnb2 in cancer surveillance . Int J Biol Markers 2010 ; 25 ( 4 ): 236 - 42 . doi: 10.5301/JBM.2010.6088 1001-9294-36-2-127/JBM.2010.6088 . DOI: 10.5301/JBM.2010.6088 http://doi.org/10.5301/JBM.2010.6088 http://journals.sagepub.com/doi/10.5301/JBM.2010.6088 http://journals.sagepub.com/doi/10.5301/JBM.2010.6088
Yamamura S , Kawakami K , Hirata H , et al . Oncogenic functions of secreted frizzled-related protein 2 in human renal cancer . Mol Cancer Ther 2010 ; 9 ( 6 ): 1680 - 7 . doi: 10.1158/1535-7163.MCT-10-0012 1001-9294-36-2-127/1535-7163.MCT-10-0012 . DOI: 10.1158/1535-7163.MCT-10-0012 http://doi.org/10.1158/1535-7163.MCT-10-0012 http://mct.aacrjournals.org/lookup/doi/10.1158/1535-7163.MCT-10-0012 http://mct.aacrjournals.org/lookup/doi/10.1158/1535-7163.MCT-10-0012
Hong Y , Huang X , An L , et al . Overexpression of COPS3 promotes clear cell renal cell carcinoma progression via regulation of phospho-AKT (Thr308), cyclin D1 and caspase-3 . Exp Cell Res 2018 ; 365 ( 2 ): 163 - 70 . doi: 10.1016/j.yexcr.2018.02.025 1001-9294-36-2-127/j.yexcr.2018.02.025 . DOI: 10.1016/j.yexcr.2018.02.025 http://doi.org/10.1016/j.yexcr.2018.02.025 https://linkinghub.elsevier.com/retrieve/pii/S0014482718301083 https://linkinghub.elsevier.com/retrieve/pii/S0014482718301083
Haddad AQ , Luo JH , Krabbe LM , et al . Prognostic value of tissue-based biomarker signature in clear cell renal cell carcinoma . BJU Int 2017 ; 119 ( 5 ): 741 - 7 . doi: 10.1111/bju.13776 1001-9294-36-2-127/bju.13776 . DOI: 10.1111/bju.13776 http://doi.org/10.1111/bju.13776 http://doi.wiley.com/10.1111/bju.2017.119.issue-5 http://doi.wiley.com/10.1111/bju.2017.119.issue-5
Wei C , Yang XL , Xi JH , et al . High expression of pituitary tumor-transforming gene-1 predicts poor prognosis in clear cell renal cell carcinoma . Mol Clin Oncol 2015 ; 3 ( 2 ): 387 - 91 . doi: 10.3892/mco.2014.478 1001-9294-36-2-127/mco.2014.478 . DOI: 10.3892/mco.2014.478 http://doi.org/10.3892/mco.2014.478 https://www.spandidos-publications.com/10.3892/mco.2014.478 https://www.spandidos-publications.com/10.3892/mco.2014.478
Pei L , Melmed S . Isolation and characterization of a pituitary tumor-transforming gene (PTTG) . Mol Endocrinol 1997 ; 11 ( 4 ): 433 - 41 . doi: 10.1210/mend.11.4.9911 1001-9294-36-2-127/mend.11.4.9911 . DOI: 10.1210/mend.11.4.9911 http://doi.org/10.1210/mend.11.4.9911
Feng ZZ , Chen JW , Yang ZR , et al . Expression of PTTG1 and PTEN in endometrial carcinoma: correlation with tumorigenesis and progression . Med Oncol 2012 ; 29 ( 1 ): 304 - 10 . doi: 10.1007/s12032-010-9775-x 1001-9294-36-2-127/s12032-010-9775-x . DOI: 10.1007/s12032-010-9775-x http://doi.org/10.1007/s12032-010-9775-x http://link.springer.com/10.1007/s12032-010-9775-x http://link.springer.com/10.1007/s12032-010-9775-x
Yoon CH , Kim MJ , Lee H , et al . PTTG1 oncogene promotes tumor malignancy via epithelial to mesenchymal transition and expansion of cancer stem cell population . J Biol Chem 2012 ; 287 ( 23 ): 19516 - 27 . doi: 10.1074/jbc.M111.337428 1001-9294-36-2-127/jbc.M111.337428 . DOI: 10.1074/jbc.M111.337428 http://doi.org/10.1074/jbc.M111.337428 https://linkinghub.elsevier.com/retrieve/pii/S0021925820500136 https://linkinghub.elsevier.com/retrieve/pii/S0021925820500136
Rahman MA , Amin ARMR , Wang X , et al . Systemic delivery of siRNA nanoparticles targeting RRM2 suppresses head and neck tumor growth . J Control Release 2012 ; 159 ( 3 ): 384 - 92 . doi: 10.1016/j.jconrel.2012.01.045 1001-9294-36-2-127/j.jconrel.2012.01.045 . DOI: 10.1016/j.jconrel.2012.01.045 http://doi.org/10.1016/j.jconrel.2012.01.045 https://linkinghub.elsevier.com/retrieve/pii/S0168365912000776 https://linkinghub.elsevier.com/retrieve/pii/S0168365912000776
Morikawa T , Hino R , Uozaki H , et al . Expression of ribonucleotide reductase M2 subunit in gastric cancer and effects of RRM2 inhibition in vitro . Hum Pathol 2010 ; 41 ( 12 ): 1742 - 8 . doi: 10.1016/j.humpath.2010.06.001 1001-9294-36-2-127/j.humpath.2010.06.001 . DOI: 10.1016/j.humpath.2010.06.001 http://doi.org/10.1016/j.humpath.2010.06.001
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621