Clinical significance of heparin-binding epidermal growth factor-like growth factor and a disintegrin and metalloprotease 17 expression in human ovarian cancer
Clinical significance of heparin-binding epidermal growth factor-like growth factor and a disintegrin and metalloprotease 17 expression in human ovarian cancer
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DOI：
10.1158/1078-0432.ccr-04-1426
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发表时间：
2005-07-01
影响因子：
11.5
通讯作者：
Nakano, H
中科院分区：
文献类型：
--
作者：
Tanaka, Y;Miyamoto, S;Nakano, H
目的：溶血磷脂酸在卵巢癌患者的腹腔液中富集，在卵巢癌的进展中起关键作用。溶血磷脂酸可以产生表皮生长因子受体（EGFR）信号反式激活，涉及ADAM（去整合素和金属蛋白酶）家族金属蛋白酶对EGFR配体的加工。我们的目的是探讨EGFR配体和ADAM家族在溶血磷脂酸诱导的卵巢癌发病机制中的临床意义。实验设计：我们检测了108例正常卵巢或卵巢癌患者中EGFR配体和ADAM家族成员的表达，采用实时荧光PCR、免疫组化和原位杂交技术，并分析这些分子的临床作用。这些数据进行统计分析，使用Mann-Whitney检验，Kaplan-Meier方法，或斯皮尔曼的相关性analysis.Results：大的差异表达肝素结合EGF样生长因子（HB-EGF）和其他EGFR配体和ADAM 17和其他ADAM家族成员。晚期卵巢癌组织中HB-EGF表达明显高于正常卵巢组织（P < 0.01）。HB-EGF表达与临床预后显著相关（P < 0.01）。ADAM 17在早期和晚期卵巢癌组织中的表达均显著高于正常卵巢组织（P均< 0.01），但对无进展生存期无临床意义。结论：HB-EGF和ADAM 17在卵巢癌的发生发展中起重要作用，HB-EGF在卵巢癌的侵袭行为中起重要作用。
Purpose: Lysophosphaticlic acid, which is enriched in the peritoneal fluid of ovarian cancer patients, plays a key role in the progression of ovarian cancer. Lysophosphaticlic acid can generate epidermal growth factor receptor (EGFR) signal transactivation involving processing of EGFR ligands by ADAM (a disintegrin and metalloprotease) family metalloproteases. We aimed to investigate the clinical significance of EGFR ligands and ADAM family in the lysophosphaticlic acid-induced pathogenesis of ovarian cancer.Experimental Design: We examined the expression of EGFR ligands and ADAM family members in 108 patients with normal ovaries or ovarian cancer, using real-time PCR, immunohistochemistry, and in situ hybridization, and analyzed the clinical roles of these molecules. Statistical analyses of these data were done using the Mann-Whitney test, Kaplan-Meier method, or Spearman's correlation analysis.Results: Large differences in expression were found for heparin-binding EGF-like growth factor (HB-EGF) and other EGFR ligands and for .ADAM 17 and other ADAM family members. HB-EGF expression was significantly increased in advanced ovarian cancer compared with that in normal ovaries (P < 0.01). HB-EGF expression was significantly associated with the clinical outcome (P < 0.01). ADAM 17 expression was significantly enhanced in both early and advanced ovarian cancer compared with that in normal ovaries (both P < 0.01), although it had no clinical significance in the progression-free survival. HB-EGF expression was significantly correlated with ADAM 17 expression (gamma = 0.437, P < 0.01).Conclusions: Our findings suggest that HB-EGF and ADAM 17 contribute to the progression of ovarian cancer and that HB-EGF plays a pivotal role in the aggressive behavior of a tumor in ovarian cancer.