Up-regulation of stromal versican expression in advanced stage serous ovarian cancer.
Up-regulation of stromal versican expression in advanced stage serous ovarian cancer.
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DOI：
10.1016/j.ygyno.2010.05.029
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发表时间：
2010-10
影响因子：
4.7
通讯作者：
Mok SC
中科院分区：
文献类型：
--
作者：
Ghosh S;Albitar L;LeBaron R;Welch WR;Samimi G;Birrer MJ;Berkowitz RS;Mok SC
本研究的目的是通过研究多功能蛋白聚糖 (VCAN) 的表达、功能及其与临床结果的相关性，探讨其在晚期浆液性卵巢癌中的作用。对从晚期浆液性卵巢癌的肿瘤和基质成分以及正常卵巢上皮组织中分离的RNA进行微阵列分析，以鉴定卵巢肿瘤基质中上调的基因。使用免疫组织化学和定量实时 PCR (Q-RT-PCR) 对上调基因之一 VCAN 进行验证研究。对浆液性卵巢肿瘤进行 VCAN (n=111) 和 CD31 (n=56) 的免疫定位。进行 CD31 染色以检查微血管密度 (MVD)。对 65 个样本进行 Q-RT-PCR 评估 VCAN 异构体的差异表达。进行细胞增殖和侵袭测定，以检查 V1 处理的卵巢癌细胞系和内皮细胞系与对照组有何不同。使用 VCAN 表达进行单变量生存分析。与 CD31、铂类耐药性和临床数据进行相关性分析。使用 Q-RT-PCR 和免疫组织化学的验证研究表明，与正常卵巢基质和卵巢癌细胞相比，卵巢癌基质中 VCAN V1 同工型表达显着升高。相关研究表明基质 VCAN 表达与较差的总体生存率和无进展生存率、铂类耐药和 MVD 增加相关。 VCAN 处理的卵巢癌和内皮细胞显示出增加的侵袭潜力。 VCAN 过度表达与 MVD 和侵袭潜力增加相关，这可能导致总体生存期和无进展生存期较差以及铂类耐药。
The purpose of this study is to examine the role of versican (VCAN) in advanced stage serous ovarian cancer by investigating its expression, its function, and its correlation with clinical outcomes. Microarray analysis was performed on RNA isolated from tumor and stromal components of advanced stage serous ovarian cancer and normal ovarian epithelial tissue to identify genes up-regulated in ovarian tumor stroma. Validation studies using immunohistochemistry and quantitative real-time PCR (Q-RT-PCR) was performed on one of the up-regulated genes, VCAN. Immunolocalization of VCAN (n=111) and CD31 (n= 56) were done on serous ovarian tumors. CD31 staining was performed to examine microvessel density (MVD). Q-RT-PCR was performed on 65 samples to evaluate the differential expression of VCAN isoforms. Cell proliferation and invasion assays were performed to examine how V1-treated ovarian cancer cell lines and an endothelial cell line would differ from controls. Univariate survival analyses were done with VCAN expression. Correlation analysis was done with CD31, platinum resistance, and clinical data. Validation studies using Q-RT-PCR and immunohistochemistry showed significantly higher VCAN V1 isoform expression in ovarian cancer stroma compared with normal ovarian stroma and ovarian cancer cells. Correlation studies showed stromal VCAN expression was associated with poorer overall and progression free survival, platinum resistance, and increased MVD. VCAN-treated ovarian cancer and endothelial cells showed increased invasion potential. VCAN overexpression is associated with increased MVD and invasion potential, which may lead to poorer overall and progression free survival and platinum resistance.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
DOI：
10.1097/00005072-199605000-00005
发表时间：
1996-05-01
影响因子：
3.2
作者：
Paulus, W;Baur, I;Zimmermann, DR
通讯作者：
Zimmermann, DR
影响因子：
3.6
作者：
AUERSPERG, N;MACLAREN, IA;KRUK, PA
通讯作者：
KRUK, PA
影响因子：
2.1
作者：
Rahmani, M;Wong, BW;McManus, BM
通讯作者：
McManus, BM
影响因子：
5.7
作者：
Zeng, Zhihong;Samudio, Ismael J.;Konopleva, Marina
通讯作者：
Konopleva, Marina