目的:检测FOXC2在肝外胆管细胞癌(EHCC)中表达的临床意义,并初步探讨FOXC2在体外对EHCC肿瘤细胞增殖、侵袭迁移和上皮间质转化的作用。方法:免疫组织化学法检测FOXC2在EHCC组织和正常胆管组织中的表达;qRT-PCR检测FOXC2 m RNA在EHCC组...目的:检测FOXC2在肝外胆管细胞癌(EHCC)中表达的临床意义,并初步探讨FOXC2在体外对EHCC肿瘤细胞增殖、侵袭迁移和上皮间质转化的作用。方法:免疫组织化学法检测FOXC2在EHCC组织和正常胆管组织中的表达;qRT-PCR检测FOXC2 m RNA在EHCC组织和正常胆管组织中的表达;分析FOXC2表达水平与患者临床病理因素和预后的关系。选择FOXC2高表达的HuCCT1细胞进行转染敲降FOXC2,CCK-8实验检测细胞增殖活力;Transwell实验检测细胞的迁移和侵袭能力;Westernblot检测上皮间质转化蛋白E-cadherin、N-cadherin、Vimentin和MMP-2的表达。结果:免疫组化结果表明,77例EHCC样本中68例(88.3%)FOXC2表达阳性。qRT-PCR检测结果表明FOXC2mRNA在EHCC组织的表达水平显著高于正常胆管上皮组织。FOXC2表达水平与EHCC患者肿瘤组织分化、临床病理分级、淋巴侵犯等相关;进一步分析发现,FOXC2高表达组患者预后较差,且FOXC2高表达是影响EHCC患者临床预后的独立危险因素。体外实验结果显示,敲降FOXC2显著降低HuCCT1细胞侵袭和迁移能力,但不改变细胞增殖活力;显著降低EMT蛋白N-cadherin、Vimentin和MMP-2的表达,促进E-cadherin的表达。结论:FOXC2在EHCC组织中的高表达促进肿瘤进展并与患者不良预后相关,可能与FOXC2促进EHCC癌细胞的侵袭、迁移和上皮间质转化有关。展开更多
Background:Adjuvant(chemo)radiotherapy(A(C)RT)may be an important supplement to surgery for extrahepatic cholangiocarcinoma(EHCC).However,whether all patients would achieve benefits from A(C)RT and which adjuvant regi...Background:Adjuvant(chemo)radiotherapy(A(C)RT)may be an important supplement to surgery for extrahepatic cholangiocarcinoma(EHCC).However,whether all patients would achieve benefits from A(C)RT and which adjuvant regimen,adjuvant radiotherapy(ART)or adjuvant chemoradiotherapy(ACRT),would be preferred,are still undetermined.The low incidence of EHCC makes it difficult to carry out randomized controlled trials(RCTs);therefore,almost all clinical studies on radiotherapy are retrospective.We have conducted a meta-analysis of these retrospective studies.Methods:We conducted a meta-analysis of current retrospective studies using PubMed,Embase,and ClinicalTrials databases.All studies published in English that were related to A(C)RT and which analyzed overall survival(OS),disease-free survival(DFS),or locoregional recurrence-free survival(LRFS)were included.Estimated hazard ratios(HRs)were calculated for OS,DFS,and LRFS.Results:Data from eight studies including 685 patients were included.Our analysis showed that A(C)RT significantly improved OS(HR 0.69,95%confidence interval(CI)0.48–0.97,P=0.03),DFS(HR 0.60,95%CI 0.47–0.76,P<0.0001),and LRFS(HR 0.27,95%CI 0.17–0.41,P<0.00001)of EHCC overall.In subgroups,patients with microscopically positive resection margin(R1)could achieve a benefit from A(C)RT(HR 0.44,95%CI 0.27–0.72,P=0.001).No statistically OS difference was observed in negative resection margin(R0)subgroup(HR 0.98,95%CI 0.30–3.19,P=0.98).Significant OS benefit was found in patients who received concurrent ACRT(HR 0.40,95%CI 0.26–0.62,P<0.0001),while the result of ART without chemotherapy showed no significant benefit(HR 1.14,95%CI 0.29–4.50,P=0.85).In the distal cholangiocarcinoma subgroup,no significant difference was seen when ACRT and ART were included(HR 0.61,95%CI 0.14–2.72,P=0.52),but a significant difference was seen ewOshSpe,enDc iaFanlSla,yl yianzn iddn igsL ttRahlF ep Sca iotinne cEnutHrsr.C eCnt pAaCtieRnTt so,nelys p(eHcRi a0 ll.y2 i9 n,t9 h5 o%s eC Iw i0 t.h13 R–10 r.e6 s4 e,cPti=o0 n.0 m0 a2 r).g iCnso.n AclCusRioT nms:aAy(bCe)RsTu pmeraiyo ri tmop rAoRvTe .展开更多
文摘目的:检测FOXC2在肝外胆管细胞癌(EHCC)中表达的临床意义,并初步探讨FOXC2在体外对EHCC肿瘤细胞增殖、侵袭迁移和上皮间质转化的作用。方法:免疫组织化学法检测FOXC2在EHCC组织和正常胆管组织中的表达;qRT-PCR检测FOXC2 m RNA在EHCC组织和正常胆管组织中的表达;分析FOXC2表达水平与患者临床病理因素和预后的关系。选择FOXC2高表达的HuCCT1细胞进行转染敲降FOXC2,CCK-8实验检测细胞增殖活力;Transwell实验检测细胞的迁移和侵袭能力;Westernblot检测上皮间质转化蛋白E-cadherin、N-cadherin、Vimentin和MMP-2的表达。结果:免疫组化结果表明,77例EHCC样本中68例(88.3%)FOXC2表达阳性。qRT-PCR检测结果表明FOXC2mRNA在EHCC组织的表达水平显著高于正常胆管上皮组织。FOXC2表达水平与EHCC患者肿瘤组织分化、临床病理分级、淋巴侵犯等相关;进一步分析发现,FOXC2高表达组患者预后较差,且FOXC2高表达是影响EHCC患者临床预后的独立危险因素。体外实验结果显示,敲降FOXC2显著降低HuCCT1细胞侵袭和迁移能力,但不改变细胞增殖活力;显著降低EMT蛋白N-cadherin、Vimentin和MMP-2的表达,促进E-cadherin的表达。结论:FOXC2在EHCC组织中的高表达促进肿瘤进展并与患者不良预后相关,可能与FOXC2促进EHCC癌细胞的侵袭、迁移和上皮间质转化有关。
基金Project supported by the National Natural Science Foundation of China(No.81402520)。
文摘Background:Adjuvant(chemo)radiotherapy(A(C)RT)may be an important supplement to surgery for extrahepatic cholangiocarcinoma(EHCC).However,whether all patients would achieve benefits from A(C)RT and which adjuvant regimen,adjuvant radiotherapy(ART)or adjuvant chemoradiotherapy(ACRT),would be preferred,are still undetermined.The low incidence of EHCC makes it difficult to carry out randomized controlled trials(RCTs);therefore,almost all clinical studies on radiotherapy are retrospective.We have conducted a meta-analysis of these retrospective studies.Methods:We conducted a meta-analysis of current retrospective studies using PubMed,Embase,and ClinicalTrials databases.All studies published in English that were related to A(C)RT and which analyzed overall survival(OS),disease-free survival(DFS),or locoregional recurrence-free survival(LRFS)were included.Estimated hazard ratios(HRs)were calculated for OS,DFS,and LRFS.Results:Data from eight studies including 685 patients were included.Our analysis showed that A(C)RT significantly improved OS(HR 0.69,95%confidence interval(CI)0.48–0.97,P=0.03),DFS(HR 0.60,95%CI 0.47–0.76,P<0.0001),and LRFS(HR 0.27,95%CI 0.17–0.41,P<0.00001)of EHCC overall.In subgroups,patients with microscopically positive resection margin(R1)could achieve a benefit from A(C)RT(HR 0.44,95%CI 0.27–0.72,P=0.001).No statistically OS difference was observed in negative resection margin(R0)subgroup(HR 0.98,95%CI 0.30–3.19,P=0.98).Significant OS benefit was found in patients who received concurrent ACRT(HR 0.40,95%CI 0.26–0.62,P<0.0001),while the result of ART without chemotherapy showed no significant benefit(HR 1.14,95%CI 0.29–4.50,P=0.85).In the distal cholangiocarcinoma subgroup,no significant difference was seen when ACRT and ART were included(HR 0.61,95%CI 0.14–2.72,P=0.52),but a significant difference was seen ewOshSpe,enDc iaFanlSla,yl yianzn iddn igsL ttRahlF ep Sca iotinne cEnutHrsr.C eCnt pAaCtieRnTt so,nelys p(eHcRi a0 ll.y2 i9 n,t9 h5 o%s eC Iw i0 t.h13 R–10 r.e6 s4 e,cPti=o0 n.0 m0 a2 r).g iCnso.n AclCusRioT nms:aAy(bCe)RsTu pmeraiyo ri tmop rAoRvTe .
