转录激活因子-4、第二个线粒体衍生的半胱氨酸蛋白酶激活剂在卵巢癌组织中的表达及临床意义

目的探讨卵巢癌组织中转录激活因子-4(ATF-4)、第二个线粒体衍生的半胱氨酸蛋白酶激活剂(SMAC)蛋白的表达情况及临床意义。方法收集90例卵巢癌患者的卵巢癌组织标本和90例卵巢良性肿瘤患者的良性肿瘤组织标本。采用免疫组化染色法检测两种组织中ATF-4、SMAC蛋白的表达情况,并对卵巢癌组织中ATF-4、SMAC蛋白表达与卵巢癌患者病理特征的关系进行分析。结果免疫组化染色结果显示,卵巢癌组织中ATF-4的阳性表达率明显高于卵巢良性肿瘤组织(P﹤0.01)。卵巢癌组织中SMAC蛋白的阳性表达率明显低于卵巢良性肿瘤组织(P﹤0.01)。FIGO分期为Ⅲ~Ⅳ期、有淋巴结转移、组织学分级为G3级的上皮性卵巢癌患者上皮性卵巢癌组织中ATF-4蛋白的阳性表达率均高于FIGO分期为Ⅰ~Ⅱ期、无淋巴结转移、组织学分级为G1~G2级的患者(P﹤0.05);FIGO分期为Ⅲ~Ⅳ期、有淋巴结转移、组织学分级为G3级的上皮性卵巢癌患者上皮性卵巢癌组织中SMAC蛋白的阳性表达率均明显低于FIGO分期为Ⅰ~Ⅱ期、无淋巴结转移、组织学分级为G1~G2级的患者(P﹤0.01);不同病灶直径的上皮性卵巢癌组织中ATF-4、SMAC蛋白的阳性表达率比较,差异均无统计学意义(P﹥0.05)。结论上皮性卵巢癌组织中ATF-4蛋白的表达上调,SMAC蛋白的表达下调,且ATF-4、SMAC蛋白表达可能与上皮性卵巢癌患者的病情进展有一定关系。     

卵巢癌组织中YB1和CD44蛋白表达及与卵巢癌患者临床特征的关系

目的探讨卵巢癌组织中Y-盒结合蛋白1(YB1)和黏附分子CD44的表达情况及与卵巢癌患者临床特征的关系。方法收集80例上皮性卵巢癌患者的上皮性卵巢癌组织标本和80例卵巢良性上皮性肿瘤患者的卵巢良性上皮性肿瘤组织标本,采用免疫组织化学染色法检测两种组织标本中YB1和CD44蛋白的表达情况,分析上皮性卵巢癌组织中YB1和CD44蛋白表达的相关性,以及YB1和CD44蛋白表达与卵巢癌患者临床特征的关系。结果上皮性卵巢癌组织中YB1和CD44蛋白的阳性表达率分别为57.50%和65.00%,均明显高于卵巢良性上皮性肿瘤组织的6.25%和10.00%,差异均有统计学意义(P﹤0.01)。相关性分析结果显示,上皮性卵巢癌组织中YB1和CD44蛋白的表达呈明显正相关(r=0.588,P﹤0.01)。国际妇产科联盟(FIGO)分期为Ⅲ～Ⅳ期、有淋巴结转移的上皮性卵巢癌患者上皮性卵巢癌组织中YB1蛋白的阳性表达率均高于FIGO分期为Ⅰ～Ⅱ期、无淋巴结转移的上皮性卵巢癌患者,FIGO分期为Ⅲ～Ⅳ期、低分化、有淋巴结转移的上皮性卵巢癌患者上皮性卵巢癌组织中CD44蛋白的阳性表达率均高于FIGO分期为Ⅰ～Ⅱ期、中/高分化、无淋巴结转移的上皮性卵巢癌患者,差异均有统计学意义(P﹤0.05)。结论上皮性卵巢癌组织中YB1和CD44蛋白表达水平明显升高,二者的表达呈正相关,且与上皮性卵巢癌患者的临床分期和淋巴结转移情况密切相关。     

HE4在上皮性卵巢癌中的表达情况及其与临床特征及预后的关系分析

目的 探讨HE4在上皮性卵巢癌中的表达情况及其与临床特征及预后的关系.方法 选取150例上皮性卵巢癌患者和72例良性卵巢疾病患者,采用酶联免疫吸附法(ELISA)检测并比较150例上皮性卵巢癌患者和72例良性卵巢疾病患者的血清HE4水平;采用免疫组织化学法(IHC)检测150例上皮性卵巢癌患者癌组织和相应癌旁正常组织中HE4的表达情况,分析其与上皮性卵巢癌临床特征的关系;随访36个月,记录并分析HE4表达与上皮性卵巢癌患者生存情况的关系.结果 上皮性卵巢癌患者的血清HE4水平明显高于良性卵巢疾病患者,上皮性卵巢癌组织中HE4蛋白的阳性表达率明显高于癌旁正常组织,差异均有统计学意义(P﹤0.01);肿瘤直径﹥3 cm、低分化、Ⅲ～Ⅳ期、有淋巴结转移的上皮性卵巢癌组织的HE4蛋白的阳性表达率分别高于肿瘤直径≤3 cm、中高分化、Ⅰ～Ⅱ期、无淋巴结转移的癌组织,差异均有统计学意义(P﹤0.05);随访36个月,HE4蛋白阳性表达的上皮性卵巢癌患者的生存率低于阴性表达的患者,差异有统计学意义(P﹤0.05).结论 HE4是上皮性卵巢癌的良好肿瘤标志物,与肿瘤的良、恶性鉴别及临床特征有密切的关系,对上皮性卵巢癌患者的早期诊断及预后有一定的价值.     

ERK1/2和cyclinD1蛋白在卵巢上皮性肿瘤组织中的表达及其意义

 目的　探讨卵巢上皮性肿瘤组织中细胞外信号调节激酶 (ERK1/ 2 )及细胞周期素D1(cyclinD1)的表达及意义。方法　应用免疫组织化学技术 ,检测 49例卵巢上皮性癌组织 ,2 6例良性卵巢上皮性肿瘤组织及 10例正常卵巢组织中ERK1/ 2和cyclinD1蛋白表达。 结果　ERK1/ 2和cyclinD1在卵巢上皮性癌组织中的表达阳性率显著高于正常卵巢组织和良性卵巢上皮性肿瘤组织 (P <0 .0 1)。Ⅲ～Ⅳ期卵巢癌组织中的ERK1/ 2和cyclinD1蛋白表达水平高于Ⅰ～Ⅱ期卵巢癌 (P <0 .0 5)。ERK1/ 2和cyclinD1蛋白表达阳性率呈明显的正相关 (P <0 .0 5)。结论　ERK 1/ 2和cyclinD1在卵巢上皮性癌发生、发展中起重要作用 ,ERK通过诱导cyclinD1蛋白过表达使卵巢上皮性癌细胞增殖和演进     

Fas/FasL系统与卵巢肿瘤的免疫逃逸的研究

目的 :检测Fas、FasL在上皮性卵巢癌及其肿瘤浸润淋巴细胞 (TIL)中的表达 ,探讨Fas系统在卵巢癌免疫逃逸中的作用。方法 :用流式细胞术检测了 31份上皮性卵巢癌、2 0份卵巢良性肿瘤、10份正常卵巢组织以及 31份卵巢癌TIL、12份卵巢良性肿瘤TIL的Fas及FasL的表达。结果 :卵巢癌组织的Fas表达明显低于卵巢良性肿瘤及正常卵巢组织 ,P <0 0 1;而其FasL表达明显高于后者 ,P <0 0 1。卵巢良性肿瘤及正常卵巢组织的Fas、FasL表达差异无显著意义 ,P >0 0 5。卵巢癌组织中含有丰富的TIL ,其Fas及FasL的表达明显高于卵巢良性肿瘤TIL ,差异有显著意义 ,P <0 0 5。卵巢癌组织Fas的表达与临床分期、组织学分级及淋巴结转移无关 ,P >0 0 5。FasL的表达与临床分期无关 ,但随组织学分级的升高而增加 ,P <0 0 5 ,有淋巴结转移者FasL的表达明显高于无淋巴结转移者 ,P <0 0 5。卵巢癌TIL中Fas及FasL的表达与各临床病理参数无关 ,P >0 0 5。结论 :上皮性卵巢癌组织中存在Fas表达的下调和FasL表达的增加 ,FasL高表达者预后不良。肿瘤细胞可能通过FasL的过度表达 ,逃避免疫监视 ,诱导Fas敏感的TIL凋亡 ,发生浸润和转移。     

TGF-β1在卵巢上皮性癌的表达水平及意义

目的：分析血清TGF—β1水平与上皮性卵巢癌发生、进展及预后的关系,探讨血清TGF—β1水平能否作为一种新的肿瘤标志物应用于卵巢癌的诊断及预后评估。方法：ELISA方法测定63例上皮性卵巢癌患者和27例正常女性的血清TGF—β1浓度。结果：卵巢癌患者血清TGF—β1的水平明显高于健康对照组（P〈0．01）;Ⅲ-Ⅳ期卵巢癌患者血清TGF—β1的水平明显高于Ⅰ-Ⅱ期患者（P〈0．01）;低分化的卵巢癌患者血清TGF—β1的水平略高于高、中分化的患者（P〉0．05）;肿瘤细胞减灭术可使血清TGF—β1浓度显著下降。结论：上皮性卵巢癌患者血清TGF—β1水平较正常女性显著增高,且与淋巴结转移、临床分期密切相关,血清TGF—β1水平可能作为一种新的肿瘤标志物应用于卵巢癌的诊断和预后评估。     

血清CA125在卵巢上皮性癌诊断和预后中的价值

目的　探讨血清CA12 5测定在卵巢上皮性癌诊断及判断预后中的价值。方法　用放射免疫法测定 82例卵巢上皮性癌术前血清CA12 5水平。结果　以血清CA12 5>35u .ml-1为异常值 ,卵巢上皮性癌检出的阳性率 ( 95 .12 % )与以>2 0 0～ 30 0u .ml-1为异常值的阳性率 ( 92 .6 8%～ 90 .2 4% )无差异 (P >0 .0 5 ) ;在卵巢上皮性癌组织类型中 ,浆液性囊腺癌和未分化癌血清CA12 5水平高于其它类型 (P均 <0 .0 5 ) ;卵巢浆液性囊腺癌临床Ⅲ -Ⅳ期、病理Ⅱ -Ⅲ级血清CA12 5明显高于临床Ⅰ -Ⅱ期和病理Ⅰ级 (P <0 .0 0 5～ <0 .0 2 )。结论　血清CA12 5>2 0 0～ 30 0u .ml-1,卵巢上皮性癌的可能性极大 ;血清CA12 5的测定有助于卵巢上皮性癌组织类型的鉴别及预后的判断。     

上皮性卵巢癌患者血清sVCAM-1水平检测的临床意义

背景与目的:以往有报道血管细胞粘附分子-1(vescularcelladhesionmolecule-1,VCAM-1)在卵巢癌组织中呈高表达。最近研究证明多种肿瘤患者血清中可溶性血管细胞粘附分子-1(sVCAM-1)浓度是升高的。本实验旨在探讨上皮性卵巢癌患者血清sVCAM-1的生物学作用。方法:用酶联免疫吸附实验分别测定130例正常人、50例良性卵巢瘤患者和67例上皮性卵巢癌患者血清sVCAM-1的浓度。结果:上皮性卵巢癌中血清sVCAM-1水平犤(897±54)μg/L,83.6%犦显著高于良性卵巢瘤犤(435±43)μg/L,8.0%犦及正常对照犤(420±40)μg/L,6.2%犦(P<0.01),Ⅱ～Ⅳ期患者犤(899±71)μg/L,93.3%犦显著高于Ⅰ期犤(571±49)μg/L,63.6%犦(P<0.05),组织学分化Ⅲ级犤(982±66)μg/L,94.8%犦显著高于Ⅰ级犤(641±51)μg/L,69.2%犦和Ⅱ级犤(768±47)μg/L,66.7%犦(P<0.01),淋巴结转移患者犤(895±58)μg/L,95.1%犦显著高于无淋巴结转移患者犤(728±47)μg/L,65.4%犦(P<0.01);卵巢癌组术后犤(532±46)μg/L,37.3%犦与术前犤(897±54)μg/L,83.6%犦比较有显著性下降(P<0.005),与卵巢癌的组织学类型未见相关性(P>0.5)。多因素分析结果表明血清sVCAM-1水平与预后无相关性。结论:动态监测血清sVCAM-1水平有望成为诊断上皮性卵巢癌及监测其复发的指标之一。     

细胞角蛋白片段抗原21-1检测对卵巢癌诊断的价值

目的　探讨血清和腹腔积液中Cyfra2 1 1水平检测对卵巢癌的诊断价值。方法　采用放射免疫分析法 ,检测 3 0例卵巢恶性肿瘤患者和 10例卵巢良性肿瘤患者血清和腹腔积液中Cyfra2 1 1的水平。 结果　卵巢恶性肿瘤组血清和腹腔积液中Cyfra2 1 1浓度显著高于卵巢良性肿瘤组 ,P均 <0 .0 1。上皮性癌和转移性腺癌患者Cyfra2 1 1含量显著高于其它组织类型 (P <0 .0 5 ,P <0 .0 1)。血清Cyfra2 1 1水平与卵巢癌临床分期显著相关 (P <0 .0 5 )。血清与腹腔积液中Cyfra2 1 1水平变化无相关性 (γ=0 .0 978,P =0 .665 )。结论　Cyfra2 1 1测定对卵巢癌的诊断具有重要临床应用价值     

上皮性卵巢癌Survivin蛋白的表达及拓扑替康对其表达的影响

目的研究上皮性卵巢癌组织中Survivin蛋白表达的差异和不同浓度拓扑替康(TPT)对卵巢癌细胞株SKOV3 Survivin蛋白表达的影响。方法应用免疫组化法检测54例上皮性卵巢癌、25例良性卵巢肿瘤及20例正常卵巢组织中Survivin蛋白的表达,分析其表达与卵巢癌恶性程度及临床病理特征的关系,用不同浓度的TPT作用于对数生长期的SKOV3细胞,检测Sur- vivin蛋白的表达。结果Survivin蛋白在上皮性卵巢癌与良性上皮性卵巢肿瘤及正常卵巢组织中的表达差异具有显著意义(P＜0．01)。Survivin蛋白的表达与临床病理特征有关,Ⅲ～Ⅳ期的表达率(78．4%)明显高于Ⅰ～Ⅱ期(41．2%)(P=0．007),且肿瘤的分化程度越低。Survivin蛋白表达越强(P=0．027)．伴有淋巴结转移者(96．7%)明显高于无淋巴结转移者(29．2%)(P＜0．01)．伴有腹水转移者(94．7%)明显高于无腹水转移者(51．4%)(P＜0．001),但是与卵巢的组织学类型无关(P=0．977)。随着TPT浓度的增加,SKOV3中Survivin蛋白表达减少(P＜0．001),各组Survivin蛋白表达差异具有统计学意义。结论Survivin蛋白的表达与卵巢癌的恶性程度有关,恶性程度越高Survivin蛋白的表达越多,而TPT作用于SKOV3细胞可以抑制其Sur- vivin蛋白的表达。     

肺癌细胞间黏附分子-1的表达及其意义

目的　探讨肺癌组织 ICAM- 1与血清 s ICAM- 1的表达及其意义。方法　应用 EL ISA与免疫组化方法检测 6 8例肺癌血清 s ICAM- 1与组织 ICAM- 1表达水平。结果　癌组织 ICAM- 1表达呈阳性 7例、强阳性 19例、阴性 4 2例 ,与正常肺组织比较差异有显著性 (P <0 .0 2 5 ) ;淋巴结转移组 ICAM- 1表达阳性率高于无转移组 (P <0 .0 1) ;腺癌 ICAM- 1阳性表达率高于鳞癌 (P<0 .0 1)。肺癌血 s ICAM- 1浓度高于对照组 (P<0 .0 1) ,淋巴结转移组s ICAM- 1浓度高于无转移组 (P<0 .0 1)。 TNM分期、组织 ICAM- 1表达与血 s ICAM- 1浓度呈正相关 (P<0 .0 1)。根治术后血 s ICAM- 1浓度低于姑息术后 (P<0 .0 1)。结论　血清 s ICAM- 1水平可以反映肺癌组织的 ICAM- 1表达变化 ,并与肿瘤负荷和疾病进展相关 ,s ICAM- 1检测可作为肺癌的一项血清学动态观察指标     

Proteomic-based identification of haptoglobin-1 precursor as a novel circulating biomarker of ovarian cancer

Screening for specific biomarkers of early-stage detection of ovarian cancer is a major health priority due to the asymptomatic nature and poor survival characteristic of the disease. We utilised two-dimensional gel electrophoresis (2DE) to identify differentially expressed proteins in the serum of ovarian cancer patients that may be useful as biomarkers of this disease. In this study, 38 ovarian cancer patients at different pathological grades (grade 1 (n=6), grade 2 (n=8) and grade 3 (n=24)) were compared to a control group of eight healthy women. Serum samples were treated with a mixture of Affigel-Blue and protein A (5 : 1) for 1 h to remove high abundance protein (e.g. immunoglobulin and albumin) and were displayed using 11 cm, pH 4-7 isoelectric focusing strips for the first dimension and 10% acrylamide gel electrophoresis for the second dimension. Protein spots were visualised by SYPRO-Ruby staining, imaged by FX-imager and compared and analysed by PDQuest software. A total of 24 serum proteins were differentially expressed in grade 1 (P<0.05), 31 in grade 2 (P<0.05) and 25 in grade 3 (P<0.05) ovarian cancer patients. Six of the protein spots that were significantly upregulated in all groups of ovarian cancer patients were identified by nano-electrospray quadrupole quadrupole time-of-flight mass spectrometry (n-ESIQ(q)TOFMS) and matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOFMS) as isoforms of haptoglobin-1 precursor (HAP1), a liver glycoprotein present in human serum. Further identification of the spots at different pathological grades was confirmed by Western blotting using monoclonal antibody against a haptoglobin epitope contained within HAP1. Immunohistochemical localisation of HAP1-like activity was present in malignant ovarian epithelium and stroma but strong immunostaining was present in blood vessels, areas with myxomatous stroma and vascular spaces. No tissue localisation of HAP1-like immunoreactivity was observed in normal ovarian surface epithelium. These data highlight the need to assess circulating concentration of HAP1 in the serum of ovarian cancer patients and evaluate its potential as a biomarker in the early diagnosis of ovarian cancer.     

Synthesis and breakdown of fibrillar collagens: concomitant phenomena in ovarian cancer.

The synthesis and degradation of type I and type III interstitial collagens releases several antigenic metabolites, whose measurement allows the metabolism of connective tissue to be evaluated under a variety of different conditions. In this study we investigated the influence of benign and malignant ovarian neoplasms on the metabolism of these collagens. The study population comprised patients with benign (n = 53), borderline (n = 6) or malignant (n = 36) ovarian neoplasms. We quantified the serum, cyst fluid and peritoneal/ascitic fluid concentrations of the amino-terminal propeptide of type I (PINP) and III (PIIINP) procollagens, indicators of the synthesis of type I and III collagen, respectively and the cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), an indicator of type I collagen degradation. Macrophage colony-stimulating factor 1 (CSF-1) concentration was also assayed as its serum level is increased in ovarian cancer and CSF-1 may be involved in the regulation of collagen metabolism. The concentration of each antigen was significantly higher in patients with malignant tumour than with benign neoplasm in each comparison, except for ICTP in peritoneal fluid and for CSF-1 in cyst fluid. The high ascitic fluid concentration of PINP, PIIINP or CSF-1 correlated with malignancy, and the low cyst fluid concentration of any of the four markers was indicative of benign tumour. Levels of CSF-1 did not correlate with the levels of any of the markers of collagen turnover. The concentration of PINP in ascites was about 50 times higher and in cyst fluid about eight times higher than that in the serum from patients with malignant tumour, whereas the respective ratios for ICTP were only 2.5 and 1.3. In such patients, the ratio of ascitic fluid to serum concentration was also about 80-fold higher for PIIINP and about 20-fold higher for PINP than for ICTP. The different distributions of PIIINP, PINP and ICTP suggests dominance of synthetic processes or retarded elimination of PIIINP and PINP in ovarian cancer. In advanced malignancies, the accumulation of PINP and PIIINP in abdominal space, possibly due to increased synthesis and/or failed resorption, may promote ascites formation. This study shows that both accelerated synthesis and breakdown of fibrillar collagens are characteristic of ovarian malignancy, and suggests that measurements of cyst fluid or ascitic fluid concentrations of collagen metabolites or CSF-1 could be used in the differential diagnosis of benign and malignant ovarian neoplasms.     

Neutrophil gelatinase-associated lipocalin (NGAL) an early-screening biomarker for ovarian cancer: NGAL is associated with epidermal growth factor-induced epithelio-mesenchymal transition

The expression of neutrophil gelatinase-associated lipocalin (NGAL) has been shown to be upregulated in ovarian cancer cells. In this study, we report that the expression of immunoreactive NGAL (irNGAL) in ovarian tumors changes with disease grade and that this change is reflected in the concentration of NGAL in peripheral blood. A total of 59 ovarian tissues including normal, benign, borderline malignant and grades 1, 2 and 3 malignant were analyzed using immunohistochemistry. irNGAL was not present in normal ovaries and the NGAL expression was weak to moderate in benign tissues. Both borderline and grade 1 tumors displayed the highest amount of NGAL expression with moderate to strong staining, whereas in grade 2 and 3 tumors, the extent of staining was significantly less (p < 0.01) and staining intensity was weak to moderate. Staining in all cases was confined to the epithelium. NGAL expression was analyzed by ELISA in 62 serum specimens from normal and different grades of cancer patients. Compared to control samples, the NGAL concentration was 2 and 2.6-fold higher in the serum of patients with benign tumors and cancer patients with grade 1 tumors (p < 0.05) and that result was consistent with the expression of NGAL performed by Western blot. NGAL expression was evaluated by Western blot in an immortalized normal ovarian cell line (IOSE29) as well as ovarian cancer cell lines. Moderate to strong expression of NGAL was observed in epithelial ovarian cancer cell lines SKOV3 and OVCA433 while no expression of NGAL was evident in normal IOSE29 and mesenchyme-like OVHS1, PEO.36 and HEY cell lines. NGAL expression was downregulated in ovarian cancer cell lines undergoing epithelio-mesenchymal transition (EMT) induced by epidermal growth factor (EGF). Downregulation of NGAL expression correlated with the upregulation of vimentin expression, enhanced cell dispersion and downregulation of E-cadherin expression, some of the hallmarks of EMT. EGF-induced EMT phenotypes were inhibited in the presence of AG1478, an inhibitor of EGF receptor tyrosine kinase activity. These data indicate that NGAL may be a good marker to monitor changes of benign to premalignant and malignant ovarian tumors and that the molecule may be involved in the progression of epithelial ovarian malignancies.     

Identification of epithelial cell adhesion molecule autoantibody in patients with ovarian cancer.

The epithelial cell adhesion molecule (Ep-CAM) exhibited an ovarian cancer:normal human ovarian surface epithelium ratio of 444. For validation studies, real-time quantitative PCR analysis and immunohistochemistry were performed in normal and malignant ovarian epithelial cell lines and tissues. To evaluate the potential of the Ep-CAM autoantibody as a tumor marker, we examined the amount of Ep-CAM autoantibody in serum samples obtained from ovarian cancer patients and normal controls by an ELISA. Real-time quantitative PCR analysis revealed significant overexpression of Ep-CAM mRNA in cancer cell lines (P < 0.001) and microdissected cancer tissues (P < 0.05), compared with that in cultured normal human ovarian surface epithelium and microdissected germinal epithelium, respectively. Immunolocalization of the Ep-CAM autoantibody showed that the sera of ovarian cancer patients expressed higher levels of Ep-CAM autoantibody than benign tumor patients and normal controls (P < 0.05). The levels of Ep-CAM autoantibody found were as follows: 0.132 in 52 patients with ovarian cancer, 0.098 in 26 cases with benign gynecologic disease, and 0.090 in 26 normal women. This investigation has shown that the Ep-CAM autoantibody was found to be associated with ovarian cancer and suggested that future research assessing its clinical usefulness would be worthwhile.     

Role of serum-derived hyaluronan-associated protein-hyaluronan complex in ovarian cancer

The objective of this study was to determine if the level of serum hyaluronan (HA), serum-derived HA-associated protein (SHAP)-HA complex, and urinary trypsin inhibitor (UTI) correlate with the clinical outcome of ovarian cancer patients. The relationship of metalloproteinase and its inhibitor with HA and the SHAP-HA complex was also examined. Serum and urine samples were obtained from 45 patients with ovarian cancer, 22 patients with benign ovarian tumors and 50 healthy women. Concentrations of serum HA and UTI were measured by an inhibitory sandwich enzyme-linked immunosorbent assay, and concentrations of the serum SHAP-HA complex were measured by a sandwich enzyme-linked immunosorbent assay. Concentrations of MMP-2, MMP-9 and TIMP-1 were measured by a one-step enzyme immunoassay. The levels of HA, SHAP-HA complex, MMP-9 and TIMP-1 were higher in the ovarian cancer group than in the benign ovarian tumor group. In ovarian cancer patients, the levels of HA, SHAP-HA complex and MMP-9 were higher in the stage III/IV group than in the stage I/II group, and the levels of SHAP-HA complex, MMP-9 and TIMP-1 were higher in the non-responder group than in the responder group. The serum concentration of SHAP-HA complex had a significant correlation with HA, MMP-9 and TIMP-1 in ovarian cancer patients. The patients with elevated SHAP-HA complex had a shorter disease-free survival compared with those with normal levels of SHAP-HA complex. The multiple regression analysis revealed that SHAP-HA complex is the significant independent variable for progression-free survival. The elevated level of SHAP-HA complex may indicate the prognosis of recurrence and reflect the tumor metastasis associated with MMP-9 in ovarian cancer patients.     

血清HE4浓度测定对卵巢恶性肿瘤的诊断价值

目的探讨血清HE4（human epididymis gene product 4,HE4）水平测定对卵巢恶性肿瘤的诊断价值。方法通过酶联免疫法（ELISA法）分别测定64例卵巢上皮性恶性肿瘤患者、40例卵巢良性肿瘤患者以及40例健康妇女血清HE4水平,同时检测CA125的测定值。结果卵巢上皮性恶性肿瘤患者血清HE4测定值为395.2±231.29 pmol/L,卵巢良性肿瘤患者血清HE4测定值为43.86±20.87 pmol/L,健康妇女血清HE4测定值为30.22±9.64 pmol/L。卵巢上皮性恶性肿瘤患者血清HE4水平与其他两组比较,差异有统计学意义（P<0.01）,卵巢上皮性恶性肿瘤患者血清HE4水平明显高于其他两组。而卵巢良性肿瘤病变组和健康妇女组血清HE4水平比较,差异无统计学意义（P>0.05）。血清HE4测定值在148.8 pmol/L时诊断值最大,其特异性为97.5%,敏感度为86.4%,ROC曲线下的面积为0.975(95%CI 0.970~1.000,P<0.001), FIGO分期、是否有远处转移及术后残余灶大小为卵巢恶性肿瘤患者生存的独立影响因素, HE4及CA125阳性或阴性、是否有淋巴结转移、腹水是否阳性、大网膜是否有转移不是卵巢恶性肿瘤患者生存的独立影响因素。结论血清HE4水平检测有助于卵巢恶性肿瘤诊断。     

卵巢癌患者血清CA125和机体免疫状态的测定

目的 :探讨卵巢癌患者血清 CA12 5和机体免疫功能的表达特征。方法 :采用流式细胞术检测患者外周血细胞 CD+ 3 、CD+ 4 、CD+ 8、CD+ 4 / CD+ 8、CD+ 1 9和 CD- 3 / CD+ ( 1 6 + 56 ) (NK细胞 )的百分率 ,采用酶联免疫法检测患者血清 CA12 5的浓度。结果 :卵巢癌患者血清 CA12 5浓度显著高于正常对照组 (P<0 .0 1) ;患者 CD+ 3 、CD+ 4 、NK+和 CD+ 1 9细胞均显著低于正常对照 (P<0 .0 5或 P<0 .0 1)。随着患者血清 CA12 5浓度的增加 ,CD+ 3 、CD+ 4 、NK+ 细胞均逐渐降低 ,并呈显著的负相关 (相关系数分别为 r1 =- 0 .95 9P<0 .0 1,r2 =- 0 .932 P<0 .0 5 ,r3=- 0 .912 P<0 .0 5 )。随着临床分期的增加 ,CA 12 5浓度逐渐增加 ,而和 CD+ 3 、CD+ 4 和 NK+ 细胞则逐渐降低 ;伴肿瘤转移患者的 CA12 5浓度显著高于未转移者 (P<0 .0 1) ,而 CD+ 3 、CD+ 4 和 NK+细胞却显著低于未转移者 (P<0 .0 5 )。结论 :卵巢癌能引起患者血清 CA12 5表达率明显上调 ,而使机体免疫功能显著下降。 CA12 5的表达与患者机体免疫状态之间以及它们与临床生物学行为之间都有一定关系。