Expression of circadian clock genes and

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1、、】】Litlekalsoyetal.BMCCancer(2016)16:549DOI10.1186/s12885-016-2580-yRESEARCHARTICLEOpenAccessExpressionofcircadianclockgenesandproteinsinurothelialcancerisrelatedtocancer-associatedgenes尿道上皮癌中昼夜节律基因和蛋白质的表达与癌症相关基因有关JorunnLitlekalsoy1,2,7*,KariRostad3,Karl-HenningKalland1,

2、4,JensG.Hostmark2,5andOleDidrikLaerum1,6AbstractBackground:Thepurposeofthisstudywastoevaluateinvasiveandmetastaticpotentialofurothelialcancerbyinvestigatingdifferentialexpressionofvariousclockgenes/proteinsparticipatinginthe24hcircadianrhythmsandtocomparethesegeneexpress

3、ionswithtranscriptionofothercancer-associatedgenes.这项研究的目的是通过调查参与24h昼夜节律的各种钟基因/蛋白质的表达差异,并比较这些基因表达与其他癌症相关基因的转录，从而评估尿路上皮癌的侵袭性和转移潜力。Methods:Twentysevenpairedsamplesoftumourandbenigntissuecollectedfrompatientswhounderwentcystectomywereanalysedandcomparedto15samplesofnormalbl

4、addertissuetakenfrompatientswhounderwentcystoscopyforbenignprostatehyperplasia(unrelateddonors).Immunohistochemicalanalysesweremadeforclockandclock-relatedproteins.Inaddition,thegene-expressionlevelsof22genes(clockgenes,caseinkinases,oncogenes,tumoursuppressorgenesandcyt

5、okeratins)wereanalysedbyreal-timequantitativePCR(qPCR).从经历膀胱切除术的患者身上收集的肿瘤和良性组织的二十七个配对样品进行分析，并与取自经历过用于良性前列腺增生的膀胱镜检查的患者（不相关供体）的正常膀胱组织的15个样品进行比较。对时钟和时钟相关蛋白进行免疫组织化学分析。另外，通过实时定量PCR（qPCR）分析22种基因（钟基因，酪蛋白激酶，致癌基因，肿瘤抑制基因和细胞角蛋白）的基因表达水平.Results:Considerableup-ordown-regulationandalt

6、eredcellulardistributionofdifferentclockproteins,areductionofcaseinkinase1A1(CSNK1A1)andincreaseofcaseinkinasealpha1E(CSNK1E)werefound.Thepatternwassignificantlycorrelatedwithsimultaneousup-regulationofstimulatorytumourmarkers,andadown-regulationofseveralsuppressorgenes.

7、Thepatternwasmainlyseeninaneuploidhigh-gradecancers.Considerablealterationswerealsofoundintheneighbouringbladdermucosa.发现不同时钟蛋白的大量上调或下调和改变的细胞分布，酪蛋白激酶1A1（CSNK1A1）的减少和酪蛋白激酶α1E（CSNK1E）的增加。该模式与刺激性肿瘤标志物的同时上调和几种抑制基因的下调显着相关。该模式主要见于非整倍体高级癌症。在相邻的膀胱粘膜中也发现了相当大的改变。Conclusions:Theclo

8、secorrelationbetweenalteredexpressionofvariousclockgenesandcommontumourmarkersinurothelialcancerindicat