血管内皮生长因子、糖类抗原199和糖类抗原125对腹腔积液良恶性的鉴别价值

血管内皮生长因子、糖类抗原199和糖类抗原125对腹腔积液良恶性的鉴别价值 word格式论文 血管内皮生长因子、糖类抗原199和糖类抗原125对腹腔积液良恶性的鉴别价 值 【摘要】 目的 了解分别或联合检测腹腔积液中血管内皮生长因子,VEGF,、糖类抗原199,CA199,和CA125对良、恶性腹腔积液的鉴别诊断价值,提高对腹腔积液的诊断水平。方法 收集各种类型腹腔积液共58例,采用酶联免疫吸附法检测VEGF含量,电化学发光法检测CA199、CA125含量。 计算 各指标独立或联合鉴别诊断腹腔积液的敏感性、特异性和准确性。结果 恶性腹腔积液组VEGF、CA199、CA125含量明显高于良性腹腔积液组,P均0.01,,结核性腹腔积液组CA125含量高于肝硬化腹腔积液组,P0.01,。卵巢癌患者的腹腔积液中VEGF、CA125水平高于胃癌、结肠癌和胰腺癌,P均0.05,,胰腺癌患者腹腔积液中CA199水平高于另外3类,但无明显差异,P0.05,。VEGF诊断恶性腹腔积液的敏感性、特异性和准确性分别为84.6,、84.4,和84.5,, CA199的敏感性、特异性和准确性分别为61.5,、78.1,、70.7,,CA125的敏感性、特异性和准确性分别为69.2,、56.3,、62.1,,而联合检测VEGF、 word格式论文 CA199和CA125的敏感性、特异性和准确性分别为92.3,、81.3,、86.2,, 其中敏感性明显高于单独检测CA199(P0.01)或CA125(P0.01)。结论 腹腔积液 中VEGF、CA199、CA125测定有助于良恶性腹腔积液的鉴别诊断,恶性腹腔 积液中VEGF、CA125的含量对恶性腹腔积液的组织来源可能有一定的鉴别诊 断作用,联合检测腹腔积液中的VEGF、CA199、CA125水平,可明显提高诊 断恶性腹腔积液的敏感性。 【关键词】 腹腔积液,血管内皮生长因子,糖类抗原199,糖类抗原125, 鉴别诊断 Abstract,Objective To investigate the value of individual or combined detections of vascular endothelial growth factor (VEGF), CA199 and CA125 in differential diagnosis between benign and malignant ascites, so as to elevate the levels of ascites diagnosis.Methods 58 cases of various ascites were collected. VEGF levels were detected by enzyme-linked immunosorbent assay (ELISA) and contents of CA199 and CA125 were determined by electrochemiluminescence method. The sensitivity, specificity and accuracy of individual or combined detections of VEGF, CA199 and CA125 in differential diagnosis were calculated.Results The levels of VEGF, CA199 and CA125 in malignant ascites were significantly higher than benign ascites (P0.01). The word格式论文 CA125 levels in tuberculous ascites group were significantly higher than cirrhotic ascites group (P0.01). The levels of VEGF and CA125 in malignant ascites of ovarian carcinoma group were obviously higher than those of gastric carcinoma, colorectal carcinoma or pancreatic cancer groups (P0.05). The levels of CA199 in malignant ascites of pancreatic cancer patients were higher than the other three groups, while there was no obvious difference (P0.05). The rate of sensitivity, specificity and accuracy of VEGF in the diagnosis of the malignant ascites was 84.6%, 84.4% and 84.5%, respectively. The rate of sensitivity, specificity and accuracy of CA199 in the diagnosis of the malignant ascites was 61.5%, 78.1% and 70.7%, respectively. While the rate of sensitivity, specificity and accuracy of CA125 was 69.2%, 56.3% and 62.1%, respectively. Combined determinations of VEGF, CA199 and CA125 showed that the rate of sensitivity, specificity and accuracy was 92.3%,81.3% and 86.2%, respectively, of which the sensitivity was apparently higher than that of determinations of CA199 (P0.01) or CA125 (P0.01) alone. Conclusion The determination of VEGF, CA199 and CA125 levels in ascites might contribute to differentiate benign ascites from malignant ascites. The concentrations of VEGF and CA125 in malignant ascites might have the certain functions in the differential diagnosis of the histological origins of the malignant ascites. Combined determinations of ascites VEGF, CA199 and CA125 levels might significantly enhance the sensitivity of malignant ascites diagnosis. word格式论文 Key words: ascites, vascular endothelial growth factor, CA199, CA125, differential diagnosis 不同疾病导致的腹腔积液其 治疗 方法和预后截然不同。故病因的鉴别,尤其是良、恶性腹腔积液的鉴别极为重要。传统的腹腔积液化验检查方法特异性和敏感性均较低。腹腔积液细胞学检查特异性高,但敏感性低,故从腹腔积液中寻找理想的肿瘤标记物已成为当前研究的热点。血管内皮生长因子(VEGF)是一种肿瘤生长、浸润和转移的指标,而在恶性腹腔积液中糖类抗原199,CA199,、糖类抗原125,CA125,的表达也明显升高。目前,分别检测此3项指标以鉴别腹腔积液的良恶性的报道较多,而对联合检测的研究相对较少,联合检测3项指标的临床意义也未完全阐明,故本研究分别应用酶联免疫吸附法、电化学发光免疫分析法检测58例患者腹腔积液中的VEGF、CA199和CA125,旨在观察不同病因腹腔积液中VEGF、CA199和CA125的水平,探讨三者在良恶性腹腔积液鉴别诊断中的价值,以及三者联合检测的临床意义。 1 资料和方法 1.1 研究对象 收集自XXXX年02月—XXXX年07月睢宁县人民 医院 腹 word格式论文 腔积液患者58例,男30例,女28例,平均年龄,52.46?11.32,岁;其中良性腹腔积液组中肝硬化腹腔积液24例,结核性腹腔积液8例,恶性腹腔积液组26例,卵巢癌8例、胃癌6例、结肠癌5例、胰腺癌4例、肝癌2例、原发性腹膜癌1例,。全部病例均经细胞学检查、病理活检、B超及CT等检查确诊。良恶性腹腔积液患者的年龄、性别比较差异无显著性(P0.05) 。 1.2 方法 1.2.1 标本采集 入院次日上午抽取腹腔积液,标本采集后,先以3000 r/min 离心10min,再取上清,按每次用量分装后立即置-20?冰箱冻存待测。 1.2.2 VEGF水平的测定 VEGF试剂盒购自深圳晶美生物工程有限公司,检测采用酶联免疫吸附法,ELISA法,,操作严格按照说明书进行。 1.2.3 CA199、 CA125水平的测定 所用检测仪器为ELECSY 2010全自动电化学发光免疫分析仪(罗氏公司),并采用该公司生产的配套试剂。正常 参考 值,CA19937 kU/L,CA12535 kU/L。 word格式论文 1.3 统计学处理 实验数据采用SPSS 13.0软件进行统计,计量资料数据以?s表示,组间比较用方差分析,计数资料不同率间比较用χ2检验。检验水准,α=0.05。 2 结 果 2.1 不同类型腹腔积液VEGF、CA199、CA125水平的比较 见表1。恶性腹腔积液组VEGF、CA199浓度明显高于肝硬化腹腔积液组和结核性腹腔积液组,P均0.01,,而肝硬化腹腔积液组和结核性腹腔积液组比较则无明显差异,P0.05,,恶性腹腔积液组CA125水平明显高于肝硬化腹腔积液组和结核性腹腔积液组,差异有显著性,P0.01,,结核性腹腔积液组CA125浓度高于肝硬化腹腔积液组,P0.01,。表1 不同类型腹腔积液VEGF、CA199、CA125水平检测结果比较 与肝硬化腹腔积液组比较,?P0.01,与结核性腹腔积液组比较,?P0.01 word格式论文 2.2 不同组织来源恶性腹腔积液间VEGF、CA199、CA125的比较 见表2。其中卵巢癌患者的腹腔积液中VEGF、CA125水平高于胃癌、结肠癌和胰腺患者,P均0.01,,而胃癌、结肠癌和胰腺癌组间比较,VEGF、CA125水平则无明显差异,P0.05,。胰腺癌患者腹腔积液中CA199水平高于另外3类,但无明显差异,P0.05,。肝癌2例、原发性腹膜癌1例因病例数少,未进行统计学比较。表2 不同组织来源恶性腹腔积液组间VEGF、CA199、CA125的检测结果 分别与胃癌、结肠癌及胰腺癌组比较,?P0.01 2.3 各指标,组合,对良恶性腹腔积液鉴别的价值 各检测指标对各型腹腔积液诊断的敏感性和特异性见表3 。据良性腹腔积液VEGF,?s,值上限,同时根据 参考 文献 ,1,,取腹腔积液VEGF阳性界值为300 ng/L,恶性腹腔积液组和良性腹腔积液组的阳性人数分别是22例和5例,即实际诊断恶性腹腔积液的敏感性、特异性和准确性分别为84.6,,22/26,、84.4,,27/32,和84.5,,49/58,,取腹腔积液CA19937 kU/L、 CA12535 kU/L为阳性诊断值,腹腔积液CA199检测恶性腹腔积液的敏感性、特异性和准确性分别为61.5,,16/26,、78.1,,25/32,、70.7,,41/58,,腹腔积液CA125检测恶性腹腔积液的敏感性、特异性和准确性分别为69.2,,18/26,、56.3,,18/32,、62.1,,36/58,,同时检测腹腔积液VEGF、CA199和CA125,其中任一指标阳性,即为联合检测阳性,所得敏感性、特异性和准确性分别为92.3,,24/26,、81.3,,26/32,、86.2,,50/58,,其中敏感性明显高于单独检测CA199(P0.01)或CA125(P0.01)。表3 各指标,组合,对良恶性腹腔积液鉴别的价值 word格式论文 3 讨 论 VEGF是血小板衍生生长因子,PDGF,家族成员之一,主要有两大生物学功能,一是增加血管通透性,是已知最强的血管通透剂,二是血管生成功能,2,。而肿瘤的生长代谢、浸润转移和复发均与肿瘤的血供密切相关。国外许多实验表明,VEGF与恶性腹腔积液形成关系密切,许多肿瘤的腹膜转移依赖于VEGF水平,3,。Akutagawa等,4,研究VEGF在腹膜播散及腹腔积液形成中的作用,发现VEGF越高,腹腔积液增长的速度越快。并且VEGF的相关拮抗物的应用已在动物实验中取得了显著效果,拮抗腹腔积液中的VEGF可抑制腹腔积液的形成。本实验结果显示,恶性腹腔积液组VEGF水平明显高于肝硬化腹腔积液组和结核性腹腔积液组,P均0.01,,同时研究还发现,卵巢癌组VEGF水平明显升高达,1042.5?216.2, ng/L,高于胃癌、结肠癌和胰腺癌组,P均0.01,,而胃癌、结肠癌和胰腺癌组间比较,VEGF和CA125水平则无明显差异,P0.05,,这可能和文献所述卵巢癌细胞存在自分泌,直接分泌大量VEGF进入腹膜腔有关。另外在2例肝癌、1例原发性腹膜癌的腹腔积液中,VEGF水平均在600 ng/L以上。这些结果提示,VEGF在恶性腹腔积液中具有较高的表达水平,恶性腹腔积液中VEGF的表达对腹腔积液的组织来源可能有一定的鉴别作用,它的检测极有可能作为恶性腹腔积液诊断的一种新方法。 word格式论文 CA199是一种糖类肿瘤相关抗原,在血液中以唾液黏蛋白形式存在,分布于胎儿胰腺、胆囊、肝、肠和正常人胰、胆管上皮等处,是存在于血循环中的胃肠相关抗原,也是常用的肿瘤免疫诊断指标,CA199在胰腺癌的阳性率为85,,95%,故也是诊断胰腺癌较为可靠的指标,5,。CA125是一种大分子糖蛋白,是卵巢癌相关抗原,CA125升高有助于卵巢癌的诊断,其敏感性与卵巢癌分期及组织学类型有关,中晚期患者CA125显著升高,浆液性癌CA125水平升高,而黏液腺癌CA125水平不高。但CA125抗原并非卵巢癌细胞所特有,单国栋等,6,报道, CA125在结核性腹腔积液患者的血清及腹腔积液中含量明显升高。本实验结果显示,恶性腹腔积液组患者腹腔积液CA199、CA125均较良性腹腔积液组高,P0.01,,表明肿瘤生物学标志物尤其是CA199、CA125系由恶性细胞合成、分泌并释放入血液或体液中的生物活性物质,通过测定其含量对肿瘤有辅助诊断价值,有助于恶性腹腔积液的诊断。同时我们还发现,胰腺癌患者腹腔积液中CA199水平略高于卵巢癌、胃癌和结肠癌组,但无明显差异,P0.05,,卵巢癌组CA125水平明显高于胃癌、结肠癌和胰腺癌组,P均0.01,,结核性腹腔积液组腹腔积液中CA125水平明显高于肝硬化腹腔积液组,提示在检测不同组织来源的恶性腹腔积液中,CA199对胰腺癌可能相对比较敏感,CA125对卵巢癌比较敏感,同时CA125除可作为相关肿瘤标志物,可能在鉴别结核性浆膜腔积液也有一定价值。 通过对VEGF、CA199和CA125 三种指标,组合,的分析显示,三者联 word格式论文 合检测不但敏感性显著提高,特异性也能保持较高水平,分别为92.3,和 81.3,,明显高于单独检测CA199(P0.01)或CA125(P0.01),另外三者联合检 测,可以互为补充,提高诊断的准确性,同时通过综合分析,还可以初步判定恶 性腹腔积液的组织来源,为进一步 治疗 提供理论依据。本研究结果提示,在良、 恶性腹腔积液的鉴别诊断中,同时检测VEGF、CA199和CA125的水平具有较 高的临床价值。 【参考文献】 ,,, 郑黎,陈卫昌,严苏,等. 检测血清与腹水血管内皮生长因子对 消化系恶性肿瘤的诊断价值,J,. 临床内科杂志,2004,21(7): 463-464. ,2, Dvorak HF, Detmar M, Claffey KP, et al. Vascular permeability factor/vascular endothelial growth factor: an important mediator of angiogenesis in malignancy and inflammation ,J,. Int Arch Allergy Immunol, 1995, 107(1-3): 233-235. ,3, Mori A, Arii S , Furutani M, et al . Soluble Flt-1 gene therapy for peritoneal metastases using HVJ-cationic liposomes ,J,. Gene Therapy, 2000, 7 (12): 1027-1033. ,4, Akutagawa N, Nishikawa A, Iwasaki M, et al. Expression of vascular word格式论文 endothelia growth factor and E-Cadherin in human ovarian cancer: association with ascites fluid accumulation and peritoneal dissemination in mouse ascites model ,J, . Caner Res, 2002, 93 (6) : 644-651. ,5, Sari R, Yildirim B, Sevinc A, et al. The importance of serum and ascites fliud alpha-fetoprotEin, carcinoembryonic antigen, CA19-9, and CA15-3 levels in differential diagnosis of ascites etiology ,J,. Hepatogastroenterology, 2001, 48(142): 1616-1621. ,6, 单国栋,金恩芸,杨铭,等. CA125与腺苷脱氨酶在结核性腹膜炎 患者中的临床意义,J,. 中华内科杂志,2006,45(11): 938-939.