間皮瘤早期診斷系統(tǒng)的建立及研究進(jìn)展

度為87%,特異性為70%[12-13]。使用電子鼻技術(shù)的準(zhǔn)確率最高(95%),GC-MA和甲狀腺轉(zhuǎn)錄因子(TTF-1)]。有研究發(fā)現(xiàn)，閉合蛋白4(Claudin-4)和黏蛋白4(MUC4)在區(qū)分間皮瘤細(xì)胞和癌細(xì)胞方面的特異度可達(dá)到100%敏感性高于MUC4[22]。具有表皮生長因子樣結(jié)構(gòu)域的心臟發(fā)育蛋白1(HEG1)在區(qū)分間皮瘤細(xì)胞和腺癌細(xì)胞方面具有100%特異性，但是某些鱗癌細(xì)胞和肉瘤細(xì)胞也會表達(dá)HEG1[23]。在有淺肌層間質(zhì)侵犯的小活檢標(biāo)本或細(xì)胞學(xué)樣本中，要的BRCA1相關(guān)蛋白1(BAP1)表達(dá)缺失和FISH技術(shù)檢測到的9p21純合子缺失對的敏感性為78%,特異性為96%,MTAP免疫組化是CDKN2A熒光原位雜交診斷間三、血清生物標(biāo)志物目前，血清生物標(biāo)志物的研究取得了很多進(jìn)展(表1),但由于缺乏足夠的生物標(biāo)志物名稱發(fā)表年份(參考文獻(xiàn))病例數(shù)量(PMe/總數(shù))AUC結(jié)果及結(jié)論MSLN水平可能與胸膜間皮瘤患者預(yù)后不血清：0.813,胸膜：0.945與對照組比較，PMe組血清0.9760.873連續(xù)測量0.857vs0.818與單獨檢測比較，SMRP,miR無OPN及Ki-67是PMe患者總體生存率的獨立指標(biāo)，注：PMe:胸膜間皮瘤；HMGBI:高遷移率族蛋白1;MSLN:間皮素；MPF:巨核細(xì)胞增強(qiáng)因子；Fibulin3;纖維蛋白3;SMRP:可1.高遷移率族蛋白1(HMGB1):HMGB1是一種促炎細(xì)胞因子，由激活的巨噬時被動釋放，相反，在病理狀態(tài)下，炎癥細(xì)胞和癌細(xì)胞可使HMGB1高乙酰化[270]。在臨界值2.00ng/ml時，血清高乙?；疕MGB1在鑒別間皮瘤患者與AEx和HC患者敏感性和特異性為100%,與Fibulin-3聯(lián)合在鑒別惡性間皮瘤患者和細(xì)胞 Me中表達(dá)，但在肉瘤樣PMe中不表達(dá)，而且在腺癌(尤其是肺)中也有明顯的3.纖維蛋白3(Fibulin-3):Fibulin-3是一種由表皮生長因子的分泌糖蛋PN被認(rèn)為是PMe診斷的有效標(biāo)記物[57]。Liu等[58]表明OPN及K確認(rèn)；(2)對CTC進(jìn)行定量分析；(3)分離出的CTC可深入進(jìn)行遺傳分析和免捕獲間皮瘤細(xì)胞，對于平足蛋白表達(dá)陽性的PMe細(xì)胞系捕獲效率接近100%,能在PMe樣本中檢測到更多的CTC[68]。Me中下調(diào)，并作為潛在的腫瘤抑制因子，在許多惡性腫瘤中都有報道，但各研究報告的結(jié)果存在差異(表2)。間皮瘤中大量下調(diào)的miRNA主要是由于染色體表2miRNA在PMe患者中的差異表達(dá)參考文獻(xiàn)腫瘤樣本來源上調(diào)miRNAMunson等Singh等四Singh等四Mozzoni等Sato等四Guled等miR-16-5p,miR-222-3p和miR-30amiR-200b,miR-200e,miR-143,miR-200a,miR-2miRNA-16,miRNA-17,miRNA-126和miRNA-let-7b*,miR-1228*,miR-195*,miR-30b*,let-7e*,miR-144*,miR-203,miRmiR-32*,miR-345,miR-483-3p,miR-584,miR-423,miR-582,miR-7-1*和mimiR-595,miR-615-3p和miR-885miR17-3p,miR-17-5p,miR-18a,miR-20m,miR-31,miR-221和miR-miR-21,miR-106a,miR-143和miR-miR-221miR-17-5pmiR-17-5p,miR-18a,miR-19b,miR-20a,miR-214,miR-497,miR-500,miR-549,miR-miR-20b,miR-25,miR-92,miR-106a,miR-146b,miR-502和miR-miR-106b,miR-7,miR-182,miR-3細(xì)胞系注：FFPe:福爾馬林固定石蠟包埋組織；“-”代表無六、問題與展望目前對PMe的確切機(jī)制及診療尚不完善，準(zhǔn)確有效的早期診斷對PMe患者預(yù)后至關(guān)重要。同時篩查一些敏感性和特異性早期診斷的分子標(biāo)志物對早期診斷PMe患者非常重要。目前呼氣分析、間皮瘤患者胸腔積液細(xì)胞學(xué)早期診斷、血清生物標(biāo)志物、免疫組織化學(xué)標(biāo)記物和miRNA等多個方面相關(guān)研究取得一定進(jìn)展，但目前尚無十分可靠的獨立篩查試驗，可以預(yù)見的是，在DNA和RNA測序、高通量RNAi(RNA干擾)和CRISPR篩選等下一代分子技術(shù)的推動下，為深入研究PMe基因組學(xué)和功能基因組學(xué)及其提供了便利，同時這方面的研究也會促進(jìn)PMe的基因診斷與治療。參考文獻(xiàn)[1]YangH,XuD,SchmidRA,etalunotherapiesinmalignantpleuralmesothelioma[J].TherAdv2020,12:1758835920971421.DOI:10.1177/1758835920971421.ds[J].BMCMedGenomics,2021,14(1):104.DOI:10.1186/s1[3]ZhouJG,ZhongH,Zhprognosticsignatureformalignantpleuralmesothelioma[Jol,2019,9:78.DOI:10.3389/fonc.2019.00078.2019,4(1):bpz014.DOI:10.1093/biomethods/bpz014.2-7163/aaa499.00022.DOI:10.1183/23120541.00022-2017.[7]LamoteK,Nackaertsahypothesis[J].CancerEpid-908.DOI:10.1158/1055-9965.EPI-13-0737.[8]BrusselmansL,ArnoutsL,Millevertadiagnosticandasystematicreview[J].TranslLungC6.DOI:10.21037/tlcr.2018.04.09.[9]deGennaroG,Dragonierierizationofexhaledbreathtodifferentiatebetweenpatientswithmalignantplueralmesotheliomafromsubjectswithsimilarprofessionalasbestosexposure[J].AnalBioanalChem,2010,398DOI:10.1007/s00216-010-4238-ynosedistinguishesexhaledbreathofpatientswithmalignantpleuralmesotheliomafromcontrols[J].LungCancer,2012,75(3):326-331.DOI:10.1016/j.lungcan.2011.08.009.[11]ChapmanEA,Thomantmesotheliomausinganelectronicnose[J].EurRespirJ,2012,40(2):448-454.DOI:10.1183/09031936.00040911.[12]LamoteK,BrinkmanP,Vandermeerpleuralmesothelioma:across-sectionalcase-controlstudy[J].Oncotarget,2017,8(53):91593-91602.DOI:10.18632/oncotarget.21335.[13]LamoteK,VynckM,Vanobilityspectrometry(MCC/IMS)[J].JBreathRes,20001.DOI:10.1088/1752-7155/10/4/046001.[14]LamoteK,VynckM,Thalignantpleuralmesothelioma:avalidationstudy[J].EurRespi017,50(6):1700919.DOI:10.1183/13993003.00919-2017.[15]ZhouY,ChenE,WuX,etal.RationelsforrapidbreathteststomJTranslRes.2017,9(11):5116-51[16]HusainAN,ColbyTlogicdiagnosisofmalignantmesothelioma2017updateoftheconsensuchPatholLabMed,2018,142(1):89-108.D[17]SheaffM.Guidelinesforthecytopathologicdiagnosisofepithioidandmixed-typemalignantmesothelcytopathology.Aproposairesupdating[J].DiagnCytopathol,2020,48(10):877-879.DOI:10.[18]ShakerN,WuD,AbidAM.Cytologyofmalignantpleuralmesothel2,50(11):532-537.DOI:10.1002/dc.25053.malignantmesotheliomaenablesearlierdiagnosisandrecognizespatientswithbetterprognosis[J].DiagnCytopathol,20[20]HjerpeA,Abd-0wnS,DobraK.Cytopathollioidandmixed-typemalignantmesothelioma:tenyperienceinrelationtointernationalguidelines[J].ArchPatholLabMed,2018,142(8):893-901.DOI:10.5858/arpa.2018-0020-RA.antpleuralmesothelioma:AmericansocietDOI:10.1200/JC0.2017.76.6394.[22]MawasAS,AmatyaVJ,KushitaniK,etal.MUC4immunohistochem-i(1):134.DOI:10.1038/s41598kemembraneproteinthatservesasadiagnosticandt38/srep45768.atingbenignfrommalignantmesothelialproliferations:arewethereyet?[J].ArchPatholLabMed,2016,140(4):318-321.DOI:10.5858/asituhybridizationindiagnosisofmalignantpleuralmesothelioma[J].ModPathol,2020,33(2):245-254.DOI:10.1038/s41379-019-0310-0.[26]CheahHM,FitzgeraldD,LouwA,etal.Hyalursmalignantmesothelioma9(1):e00694.DOI:10.1002/rcr2.694.tictargetininflammato18,22(3):263-277.DOI:10.1080/14728222.2018.1439924.[28]AnderssonU,YangH,HarrisH.HigeminImmunol,2018,38:40-48.DOI:10.1016/j.smim.2018.02.011.[29]WangY,JiangZ,YanJ,etal.HMGB1asapodtherapeutictargetformalignantmesothelioma9,2019:4183157.DOI:10.1155/2019/4183157.[30]YingS,JiangZ,HeX,etal.SerumHMGB1asapotentialbiomark2017:5756102.DOI:10.1155/2017/5756102.[31]NapolitanoA,AntoineDJ,PellegriniL,eteracetylatedisoformareetectasbestosexposureandtoidentifymesotheliomapatiennCancerRes,2016,22(12):3087-3096.DOI:10.1158/1[33]PellegriniL,XueJ,LarsonD,etal.Htarget,2017,8(14):22649-22661.DOI:10.18632/oncotarget.15152.11.DOI:10.1186/s4036[35]LiY,TianW,Zhangr[J].FrontOncol,2022,12:830570.DOI:10.3389/fonc.2022.830570.etingvaccineforlungcancerimmuno13:925217.DOI:10.3389/fim[37]TsaoAS,LindwasserOW,AdjeiAA,etal.Currengementofmalignantmesothelioma:aconslcancerinstitutethoraci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