notch1通路活性分子n1ic与乳腺癌变、进展的相关性分析word论文.docxVIP

摘要目的：研究乳腺癌旁正常组织(NCAT)、导管普通型增生(UDH)、导管原位癌(DCIS)、浸润性导管癌(IDC)中Notch1信号通路活性分子N1IC、Snail蛋白表达情况，分析其表达变化在乳腺癌变、进展中的意义。方法：运用基于组织芯片的免疫组化Envision法检测200例乳腺浸润性导管癌、32例导管原位癌、40例导管普通型增生及37例癌旁正常组织中N1IC、Snail蛋白表达，比较各分子在四种乳腺组织中的表达差异，并结合课题组前期EMT相关研究，分析乳腺癌中N1IC、Snail及EMT相关分子间的相关性。结果：(1)乳腺癌旁正常组织(NCAT)、导管普通型增生(UDH)、导管原位癌(DCIS)、浸润性导管癌(IDC) 中N1IC高表达率分别为56.8%,10.0%,65.7%,75.0%;Snail高表达率分别为43.2%,55.0%,56.3,62.0%。N1IC、Snial蛋白表达在四组乳腺组织中表达水平比较，差异具有统计学意义(P0.05)。(2) 结合临床病理特征分析，结果显示乳腺癌中N1IC表达水平与患者淋巴结转移显著相关(P0.001), Snail表达水平与肿瘤淋巴结转移(P=0.01)及TNM分期(P=0.013)显著相关。(3)结合前期相关研究结果发现乳腺癌变过程中N1IC表达与Notch1表达趋势一致，均呈逐渐升高趋势，且乳腺癌中N1IC 表达与Snail表达呈显著正相关性(r=0.143,P=0.044),与E-cadherin呈显著负相关(r=-0.507,P0.001)，与N-cadherin呈显著正相关(r=0.170,P=0.016)。结论：(1)Notch1、N1IC、Snail在乳腺癌变过程中表达逐渐升高，提示其高表达促进了乳腺癌变。（2）N1IC、Snail高表达与淋巴结转移成正相关，Snail高表达与肿瘤高分期呈正相关，可能促进了乳腺癌进展。（3）Notch1-N1IC-Snail-EMT信号可能在乳腺癌的侵袭转移中发挥重要作用。关键词：乳腺浸润性导管癌；N1IC；Snail；Notch1信号通路AbstractObjective:ToexplorethesignificanceofN1ICandSnailinthedevelopmentofbreastcarcinoma,theproteinexpressionsofN1ICinactivatedNotch1signalingpathwayandSnailwereanalyzedinnormalcancerousadjacenttissue(NCAT),usualductalhyperplasia(UDH),ductalcarcinomainsitu(DCIS)andinfiltratingductalcarcinoma(IDC),respectively.Methods:Formalin-fixedparaffin-embeddedsamplesfrom200untreatedprimaryinvasiveductalcarcinomas,32ductalcarcinomasinsitu,40usualductalhyperplasiasand37adjacentnon-neoplastictissueswereexamined.ExpressionsofN1ICandSnailweremeasuredbyimmunohistochemistryontissuemicroarraystostudythedifference.ThecorrelationsamongN1IC,SnailandEMT-relatedmarkerswerefurtheranalyzedbasedontheresultsofpreviousresearch.Results:(1)ThepercentageofhighpressioninNCAT,UDH,DCISandIDCwas56.8%,10.0%,65.7%, 75.0%forN1ICand43.2%,55.0%,56.3,62.0%forSnail,respectively.Asignificantdifferencefortheexpressionofeachstudiedmarkerwasobservedinoverallcomparison(P0.05).(2)Theresultsbasedon clinicopathologicfeaturesrevealedthattheexpressionofN1ICwassignificantlyassociatedlymphnodemetastasisinbreastcancerpatients(P0.001),andtheexpressiono