间皮瘤早期诊断系统的建立及研究进展

度为87%,特异性为70%[12-13]。使用电子鼻技术的准确率最高(95%),GC-MA和甲状腺转录因子(TTF-1)]。有研究发现，闭合蛋白4(Claudin-4)和黏蛋白4(MUC4)在区分间皮瘤细胞和癌细胞方面的特异度可达到100%敏感性高于MUC4[22]。具有表皮生长因子样结构域的心脏发育蛋白1(HEG1)在区分间皮瘤细胞和腺癌细胞方面具有100%特异性，但是某些鳞癌细胞和肉瘤细胞也会表达HEG1[23]。在有浅肌层间质侵犯的小活检标本或细胞学样本中，要的BRCA1相关蛋白1(BAP1)表达缺失和FISH技术检测到的9p21纯合子缺失对的敏感性为78%,特异性为96%,MTAP免疫组化是CDKN2A荧光原位杂交诊断间三、血清生物标志物目前，血清生物标志物的研究取得了很多进展(表1),但由于缺乏足够的生物标志物名称发表年份(参考文献)病例数量(PMe/总数)AUC结果及结论MSLN水平可能与胸膜间皮瘤患者预后不血清：0.813,胸膜：0.945与对照组比较，PMe组血清0.9760.873连续测量0.857vs0.818与单独检测比较，SMRP,miR无OPN及Ki-67是PMe患者总体生存率的独立指标，注：PMe:胸膜间皮瘤；HMGBI:高迁移率族蛋白1;MSLN:间皮素；MPF:巨核细胞增强因子；Fibulin3;纤维蛋白3;SMRP:可1.高迁移率族蛋白1(HMGB1):HMGB1是一种促炎细胞因子，由激活的巨噬时被动释放，相反，在病理状态下，炎症细胞和癌细胞可使HMGB1高乙酰化[270]。在临界值2.00ng/ml时，血清高乙酰化HMGB1在鉴别间皮瘤患者与AEx和HC患者敏感性和特异性为100%,与Fibulin-3联合在鉴别恶性间皮瘤患者和细胞 Me中表达，但在肉瘤样PMe中不表达，而且在腺癌(尤其是肺)中也有明显的3.纤维蛋白3(Fibulin-3):Fibulin-3是一种由表皮生长因子的分泌糖蛋PN被认为是PMe诊断的有效标记物[57]。Liu等[58]表明OPN及K确认；(2)对CTC进行定量分析；(3)分离出的CTC可深入进行遗传分析和免捕获间皮瘤细胞，对于平足蛋白表达阳性的PMe细胞系捕获效率接近100%,能在PMe样本中检测到更多的CTC[68]。Me中下调，并作为潜在的肿瘤抑制因子，在许多恶性肿瘤中都有报道，但各研究报告的结果存在差异(表2)。间皮瘤中大量下调的miRNA主要是由于染色体表2miRNA在PMe患者中的差异表达参考文献肿瘤样本来源上调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细胞系注：FFPe:福尔马林固定石蜡包埋组织；“-”代表无六、问题与展望目前对PMe的确切机制及诊疗尚不完善，准确有效的早期诊断对PMe患者预后至关重要。同时筛查一些敏感性和特异性早期诊断的分子标志物对早期诊断PMe患者非常重要。目前呼气分析、间皮瘤患者胸腔积液细胞学早期诊断、血清生物标志物、免疫组织化学标记物和miRNA等多个方面相关研究取得一定进展，但目前尚无十分可靠的独立筛查试验，可以预见的是，在DNA和RNA测序、高通量RNAi(RNA干扰)和CRISPR筛选等下一代分子技术的推动下，为深入研究PMe基因组学和功能基因组学及其提供了便利，同时这方面的研究也会促进PMe的基因诊断与治疗。参考文献[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:aconslcancerinstitutethoracicmalignancysteeringcommittenalassociationedresearchfoundation[J].JThoraiomedicines.2021,9(4):397.DOI:10.3390/biomedicines9040397.[39]HeX,WangL,RiedelH,etal.Mesothelinprommesoth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