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

Role of serum-derived hyaluronan-associated protein-hyaluronan complex in ovarian cancer.
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DOI:
10.3892/or.19.5.1245
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发表时间:
2008-05
期刊:
影响因子:
4.2
通讯作者:
Yukihiko Obayashi;H. Yabushita;Kouhei Kanyama;M. Noguchi;Lisheng Zhuo;K. Kimata;A. Wakatsuki
Yukihiko Obayashi;H. Yabushita;Kouhei Kanyama;M. Noguchi;Lisheng Zhuo;K. Kimata;A. Wakatsuki
中科院分区:
医学3区
文献类型:
--
作者:
Yukihiko Obayashi;H. Yabushita;Kouhei Kanyama;M. Noguchi;Lisheng Zhuo;K. Kimata;A. Wakatsuki

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本研究的目的是确定血清透明质酸(HA)、血清衍生HA相关蛋白(SHAP)-HA复合物和尿胰蛋白酶抑制剂(UTI)水平是否与卵巢癌患者的临床预后相关。研究了金属蛋白酶及其抑制剂与HA和SHAP-HA复合物的关系。从45例卵巢癌患者、22例良性卵巢肿瘤患者和50例健康妇女中采集血清和尿液样本。采用抑郁性三明治酶联免疫吸附法测定血清HA和UTI的浓度,采用三明治酶联免疫吸附法测定血清sha -HA复合物的浓度。采用一步酶免疫分析法测定MMP-2、MMP-9和TIMP-1的浓度。卵巢癌组HA、SHAP-HA复合物、MMP-9、TIMP-1水平均高于卵巢良性肿瘤组。在卵巢癌患者中,III/IV期患者HA、SHAP-HA复合物和MMP-9水平高于I/II期患者,无应答组患者SHAP-HA复合物、MMP-9和TIMP-1水平高于应答组。卵巢癌患者血清SHAP-HA复合物浓度与HA、MMP-9、TIMP-1有显著相关性。与SHAP-HA复合物水平正常的患者相比,SHAP-HA复合物水平升高的患者无病生存期较短。多元回归分析显示,SHAP-HA复合物是无进展生存期的重要自变量。SHAP-HA复合物水平的升高可能预示卵巢癌患者复发的预后,并反映与MMP-9相关的肿瘤转移情况。
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.