分支DNA技术检测胃癌患者血清游离DNA的应用价值
분지DNA기술검측위암환자혈청유리DNA적응용개치
Study of serum cell free DNA in patients with gastric cancer by branched DNA
  • 万方数据
    中华检验医学杂志 중화검험의학잡지
    CHINESE JOURNAL OF LABORATORY MEDICINE
    2013年 8期 699-703 ,共5页

    吴晓燕%张金业%钱晨%景蓉蓉%戚菁%施维%张鲁榕%王志伟%鞠少卿

    오효연%장금업%전신%경용용%척정%시유%장로용%왕지위%국소경

    胃肿瘤%DNA%分支DNA信号扩增试验 胃腫瘤%DNA%分支DNA信號擴增試驗
    위종류%DNA%분지DNA신호확증시험
    Stomach neoplasms%DNA%Branched DNA signal amplification assay
    目的 分析探讨分支DNA(branched DNA,bDNA)技术定量检测胃癌患者血清游离DNA(cell free DNA,cf-DNA)水平与临床病理特征间的关系,及其在胃癌辅助诊断中的应用价值.方法 病例对照研究.收集2011年9月至2012年2月南通市肿瘤医院经病理诊断确诊的99例胃癌患者和100名健康人血清标本,2010年3月至2012年2月南通大学附属医院经病理诊断确诊的32例胃良性肿瘤患者血清标本.用bDNA技术检测其cf-DNA浓度,化学发光法检测其癌胚抗原(CEA)、糖抗原(CA)19-9、CA50、CA72-4含量.用Dunn's检验比较胃癌组与对照组(良性肿瘤、健康人)cf-DNA含量的差异；绘制受试者工作特征(ROC)曲线评估上述5项指标诊断胃癌的效能；Mann-Whitney检验分析血清cf-DNA浓度与患者性别、年龄的相关性；Kruskal-Wallis检验分析血清cf-DNA浓度与患者肿瘤部位、肿瘤分化程度、肿瘤淋巴转移分类(AJCC)分期的相关性.结果 胃癌组、胃良性肿瘤组和健康对照组血清cf-DNA含量分别为2316.0(1028.7 ～ 3742.1)、423.3 (256.3～519.2)、317.5(172.5 ～499.7) μg/L,胃癌组cGDNA含量显著高于胃良性肿瘤组(q=7.612,P＜0.01)及健康对照组(q =7.062,P＜0.01),而胃良性肿瘤组与健康对照组差异无统计学意义(q =0.598,P＞0.05).胃癌患者血清cf-DNA含量在不同年龄(t=1388.000)、性别(t=845.000)、肿瘤部位(H=3.471)、肿瘤分化程度(H=0.288)、MCC分期分组(H=6.053)间的差异无统计学意义(P均＞0.05).胃癌组血清cf-DNA与CEA、CA19-9、CA50、CA72-4无相关性(R2值分别为0.0385、0.0159、0.0029、0.0079,P均＞0.05).当上述5项指标的最佳诊断临界值分别为973.6 μg/L、4.0μg/L、32.8 kU/L、12.8 kU/L、5.1 kU/L时,胃癌组血清cf-DNA的ROC曲线下面积及诊断敏感度[0.94,76.8％ (76/99)]均高于血清CEA [0.66,31.3％ (31/99)]、CA19-9 [0.63,16.2％ (16/99)]、CA50[0.83,44.4％ (44/99)]、CA72-4 [0.67,35.4％ (35/99)]；血清cf-DNA特异度[96％ (96/100)]与血清CEA[98％ (98/100)]、CA19-9[78％ (78/100)]、CA50[97％ (97/100)]、CA72-4[98％ (98/100)]较接近.结论 bDNA技术定量检测胃癌患者血清cf-DNA比血清CEA、CA19-9、CA50、CA72-4有较高敏感度及特异度.且对胃癌辅助诊断有一定的指导和应用价值.
    목적 분석탐토분지DNA(branched DNA,bDNA)기술정량검측위암환자혈청유리DNA(cell free DNA,cf-DNA)수평여림상병리특정간적관계,급기재위암보조진단중적응용개치.방법 병례대조연구.수집2011년9월지2012년2월남통시종류의원경병리진단학진적99례위암환자화100명건강인혈청표본,2010년3월지2012년2월남통대학부속의원경병리진단학진적32례위량성종류환자혈청표본.용bDNA기술검측기cf-DNA농도,화학발광법검측기암배항원(CEA)、당항원(CA)19-9、CA50、CA72-4함량.용Dunn's검험비교위암조여대조조(량성종류、건강인)cf-DNA함량적차이；회제수시자공작특정(ROC)곡선평고상술5항지표진단위암적효능；Mann-Whitney검험분석혈청cf-DNA농도여환자성별、년령적상관성；Kruskal-Wallis검험분석혈청cf-DNA농도여환자종류부위、종류분화정도、종류림파전이분류(AJCC)분기적상관성.결과 위암조、위량성종류조화건강대조조혈청cf-DNA함량분별위2316.0(1028.7 ～ 3742.1)、423.3 (256.3～519.2)、317.5(172.5 ～499.7) μg/L,위암조cGDNA함량현저고우위량성종류조(q=7.612,P＜0.01)급건강대조조(q =7.062,P＜0.01),이위량성종류조여건강대조조차이무통계학의의(q =0.598,P＞0.05).위암환자혈청cf-DNA함량재불동년령(t=1388.000)、성별(t=845.000)、종류부위(H=3.471)、종류분화정도(H=0.288)、MCC분기분조(H=6.053)간적차이무통계학의의(P균＞0.05).위암조혈청cf-DNA여CEA、CA19-9、CA50、CA72-4무상관성(R2치분별위0.0385、0.0159、0.0029、0.0079,P균＞0.05).당상술5항지표적최가진단림계치분별위973.6 μg/L、4.0μg/L、32.8 kU/L、12.8 kU/L、5.1 kU/L시,위암조혈청cf-DNA적ROC곡선하면적급진단민감도[0.94,76.8％ (76/99)]균고우혈청CEA [0.66,31.3％ (31/99)]、CA19-9 [0.63,16.2％ (16/99)]、CA50[0.83,44.4％ (44/99)]、CA72-4 [0.67,35.4％ (35/99)]；혈청cf-DNA특이도[96％ (96/100)]여혈청CEA[98％ (98/100)]、CA19-9[78％ (78/100)]、CA50[97％ (97/100)]、CA72-4[98％ (98/100)]교접근.결론 bDNA기술정량검측위암환자혈청cf-DNA비혈청CEA、CA19-9、CA50、CA72-4유교고민감도급특이도.차대위암보조진단유일정적지도화응용개치.
    Objective To quantify cell free DNA (cf-DNA) in blood of patients with gastric cancer by a branched DNA (bDNA)-based Alu assay and analyze the relationship between serum cf-DNA levels and clinical and pathological features as well as the applicational value of the aided diagnosis of cf-DNA in GC.Methods A case-control study was conducted.Ninety-nine patients with GC diagnosed by pathological diagnosis and 100 normal controls presenting to the Nantong tumor hospital from September 2011 to February 2012 were recruited.Thirty-two patients with gastric benign tumor presenting to the Affiliated Hospital of Nantong University from March 2010 to February 2012 were also recruited.The concentration of cf-DNA was detected by bDNA and the concetrations of carcinoembryonic antigen (CEA),carcinoembryonic antigen 19-9 (CA19-9),carcinoembryonic antigen 50 (CA50),and carcinoembryonic antigen 72-4 (CA72-4) were assayed by chemiluminescence.The Dunn's test was used to compare the difference of cf-DNA between patients with GC and control groups (gastric benign tumor and healthy individuals).The diagnostic value of the five indicators was evaluated by drawing the Receiver Operating Characteristic curves (ROC).The MannWhitney test was used to analyze the difference of cf-DNA levels of the patient's gender and age.KruskalWallis test was used to compare cf-DNA correlation with the patient's tumor site,tumor differentiation,American Joint Committee on Cancer.Results The levels of cf-DNA in patients with GC,patients with gastric benign tumor and healthy individuals were 2316.0 (1028.7-3742.1),423.3 (256.3-519.2),317.5 (172.5-499.7) μg/L,respectively.There were significant differences between GC patients and gastric benign tumor patients (q =7.612,P ＜0.0001),GC patients and healthy individuals (q =7.062,P ＜0.0001),and there was no significant difference between gastric benign tumor patients and healthy individuals (q =0.598,P =0.2672).No statistically significant difference of cf-DNA in age (t =1388.000,P=0.800),gender (t =845.000,P=0.962),tumor sites (H=3.471,P=0.325) and tumor differentiation (H=0.288,P=0.866),AJCC stage (H=6.053,P =0.109) was found.There was no correlation between cf-DNA and CEA,CA19-9,CA50 and CA72-4 (R2 values were 0.0385,0.0159,0.0029,0.0079,respectively.P ＞ 0.05).The optimal diagnostic thresholds of the five indicators were 973.6 μg/L,4.0 μg/L,32.8 kU/L,12.8 kU/L,5.1 kU/L,respectively.The areas under the ROC curves and sensitivity assessing cf-DNA level [0.94,76.8％ (76/99)] were significantly larger than traditional indicators of serum CEA [0.66,31.3％ (31/99)],CA19-9 [0.63,16.2％ (16/99)],CA50 [0.83,44.4％ (44/99)],CA72-4 [0.67,35.4％ (35/99)] for GC patients.Specificity of cf-DNA [96％ (96/100)] was closer to traditional indicators of serum CEA [98 ％ (98/100)],CA19-9 [78 ％ (78/100)],CA50 [97％ (97/100)],CA72-4[98％ (98/100)].Conclusions cf-DNA levels detected by bDNA are higher specificity and better sensitivity than traditional tumor markers(CEA,CA19-9,CA50,CA72-4)for GC patients.Certain guiding significance and application value was existed by detecting cf-DNA level in the serum of GC patients.
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