Tassi R A, Bignotti E, Falchetti M, Ravanini M, Calza S, Ravaggi A, Bandiera E, Facchetti F, Pecorelli S, Santin A D
Division of Gynecologic Oncology, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy.
Int J Gynecol Cancer. 2008 Nov-Dec;18(6):1262-71. doi: 10.1111/j.1525-1438.2008.01194.x. Epub 2008 Feb 19.
Claudin-7 (CLDN-7) is a tight junction protein recently found highly differentially expressed in ovarian carcinoma. To evaluate its potential as a novel biomarker, in this study, we quantified and compared claudin-7 expression at messenger RNA and protein level in 110 patients harboring various histologic types of epithelial ovarian carcinomas (EOC). CLDN-7 transcript was found significantly overexpressed in both primary and metastatic EOCs compared to normal human ovarian surface epithelium cell lines (fold change = 111.4, P < 0.001) by reverse transcription-polymerase chain reaction. At the protein level, CLDN-7 expression was found significantly higher in tumors of primary and metastatic origin when compared to normal ovaries (P < 0.001), regardless of the histologic type, the grade of differentiation, and the pathologic stage of the disease (P = 0.12). Moreover, a strong immunoreactivity for CLDN-7 was detected in EOC cells present in ascites fluids, whereas ascites-derived inflammatory cells, histiocytes, and reactive mesothelial cells were negative. Finally, immunohistochemical expression of CLDN-7 was observed in several human normal epithelial control tissues analyzed. CLDN-7 is significantly overexpressed in all main histologic types of EOC and in single neoplastic cells disseminated in peritoneal cavity and pleural effusions, suggesting its potential role as novel diagnostic marker in ovarian cancer. Despite widespread expression of CLDN-7 in several human normal tissues, the high density of CLDN-7 molecules, their membranous localization on EOC cells, and their lack of expression on the celomic epithelium in the peritoneal cavity suggest that this target could be potentially suitable for antibody-mediated localized therapies of ovarian adenocarcinoma.
紧密连接蛋白7（CLDN - 7）是一种最近发现的在卵巢癌中高度差异表达的紧密连接蛋白。为了评估其作为一种新型生物标志物的潜力，在本研究中，我们对110例患有各种组织学类型上皮性卵巢癌（EOC）的患者，在信使核糖核酸和蛋白质水平上对紧密连接蛋白7的表达进行了定量和比较。通过逆转录 - 聚合酶链反应发现，与正常人卵巢表面上皮细胞系相比，CLDN - 7转录本在原发性和转移性EOC中均显著过表达（倍数变化 = 111.4，P < 0.001）。在蛋白质水平上，与正常卵巢相比，无论疾病的组织学类型、分化程度和病理分期如何（P = 0.12），原发性和转移性肿瘤中CLDN - 7的表达均显著更高（P < 0.001）。此外，在腹水液中的EOC细胞中检测到对CLDN - 7的强免疫反应性，而腹水来源的炎性细胞、组织细胞和反应性间皮细胞均为阴性。最后，在分析的几种人类正常上皮对照组织中观察到CLDN - 7的免疫组化表达。CLDN - 7在所有主要组织学类型的EOC以及散布在腹腔和胸腔积液中的单个肿瘤细胞中均显著过表达，表明其在卵巢癌中作为新型诊断标志物的潜在作用。尽管CLDN - 7在几种人类正常组织中广泛表达，但CLDN - 7分子的高密度、它们在EOC细胞上的膜定位以及它们在腹腔体腔上皮上的缺乏表达表明，该靶点可能潜在适用于卵巢腺癌的抗体介导的局部治疗。
