Changes in Nucleolin Expression during Malignant Transformation Leading to Ovarian High-Grade Serous Carcinoma.
Changes in Nucleolin Expression during Malignant Transformation Leading to Ovarian High-Grade Serous Carcinoma.
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卵巢癌（OVCA）是最致命的妇科恶性肿瘤之一，大多数病例发现于晚期。死亡率高的部分原因是缺乏有效的早期检测。肿瘤的发展和进展与组织蛋白表达的增加和/或它们释放到循环中有关。这些蛋白可能为OVCA的早期检测提供潜在的标志物。核仁素，一种核蛋白，就是这样一种标记物。本初步研究通过使用存档的临床样本和自发性OVCA的蛋鸡模型来检查核仁素的组织表达及其血清水平的变化是否与OVCA的发展和进展相关。核仁素被发现在卵巢和菌毛与肿瘤和血清水平相比，那些没有OVCA的高度表达。这项研究还发现，甚至在肿瘤在卵巢或伞毛中形成可检测到的实性肿块之前，肿瘤相关的血清核仁素水平就会增加，这表明核仁素可能参与恶性转化。较小的样本量是本研究的局限性;然而，它将为较大队列的临床研究奠定基础，以检查核仁素作为早期检测OVCA的潜在血清标志物的有效性。目的：卵巢高级别浆液性癌（HGSC）是一种严重的女性恶性肿瘤。核蛋白表达的改变是恶性转化的早期步骤;核仁素就是这样一种蛋白。卵巢HGSC发育过程中核仁素表达和循环水平的变化尚不清楚。本研究的目的是确定核仁素的组织和循环水平是否因恶性转化而改变，从而导致卵巢HGSC。研究方法：在探索性和前瞻性研究中，通过免疫组织化学、免疫印迹、基因表达和免疫测定，检查了健康受试者的血清、卵巢和BRCA+菌毛，以及患者（各n = 10）、健康母鸡和HGSC母鸡的血清和肿瘤组织的核仁素表达，并通过方差分析（ANOVA）进行分析。结果：核仁素在卵巢HGSC患者、母鸡及有HGSC危险的妇女中的表达均高于正常人（P < 0.05）。与正常人（1400 ± 105 pg/mL，n = 8）相比，早期（n = 5）和晚期（n = 5）HGSC患者的血清核仁素水平分别高1.5和1.7倍。此外，血清核仁素水平在可检测到的肿块形成之前显著升高（P < 0.05）。结论：这项初步研究得出结论，核仁素的组织和血清水平增加与卵巢和菌毛的恶性变化相关，导致卵巢HGSC。
Ovarian cancer (OVCA) is one of the most fatal gynecologic malignancies with most cases detected in late stages. High mortality rates are due, in part, to the lack of an effective early detection test. Tumor development and progression are associated with an increase in the expression of tissue proteins and/or their release into circulation. These proteins may offer potential markers for the early detection of OVCA. Nucleolin, a nuclear protein, is one such marker. This pilot study examined whether the tissue expression of nucleolin and its serum levels change in association with OVCA development and progression by using archived clinical samples and the laying hen model of spontaneous OVCA. Nucleolin was found to be highly expressed in ovaries and fimbriae with tumors and in serum levels compared to those without OVCA. This study also found that tumor-associated serum levels of nucleolin increase even before the tumor forms a detectable solid mass in the ovary or fimbria, suggesting that nucleolin may be involved in malignant transformation. A smaller sample size is a limitation of this study; however, it will lay the foundation for clinical studies with larger cohorts to examine the efficacy of nucleolin as a potential serum marker for the early detection of OVCA. Objective: Ovarian high-grade serous carcinoma (HGSC) is a fatal malignancy of women. Alterations in the expression of nuclear proteins are early steps in malignant transformation; nucleolin is one such protein. Changes in nucleolin expression and circulatory levels during ovarian HGSC development are unknown. The study goal was to determine if tissue and circulatory levels of nucleolin change in response to malignant transformation leading to ovarian HGSC. Methods: Sera, ovaries, and BRCA+ fimbria from healthy subjects, and sera and tumor tissues from patients (n = 10 each), and healthy hens and hens with HGSC were examined in exploratory and prospective studies for nucleolin expression by immunohistochemistry, immunoblotting, gene expression, and immunoassay, and analyzed by analysis of variance (ANOVA). Results: Compared with normal, nucleolin expression was higher in patients and hens with ovarian HGSC and in women with a risk of HGSC (P < 0.05). Compared with normal (1400 + 105 pg/mL, n = 8), serum nucleolin levels were 1.5 and 1.7-fold higher in patients with early- (n = 5) and late-stage (n = 5) HGSC, respectively. Additionally, serum nucleolin levels increased significantly (P < 0.05) prior to the formation of detectable masses. Conclusion: This pilot study concluded that tissue and serum levels of nucleolin increase in association with malignant changes in ovaries and fimbriae leading to ovarian HGSC.
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影响因子：
--
作者：
Denais C;Lammerding J
通讯作者：
Lammerding J
DOI：
10.1073/pnas.84.6.1472
发表时间：
1987-03-01
影响因子：
11.1
作者：
LAPEYRE, B;BOURBON, H;AMALRIC, F
通讯作者：
AMALRIC, F
影响因子：
11.2
作者：
Gilles, Maud-Emmanuelle;Maione, Federica;Cascone, Ilaria
通讯作者：
Cascone, Ilaria
影响因子：
1.6
作者：
Chen Z;Xu X
通讯作者：
Xu X
影响因子：
3.2
作者：
Chalfin, Heather J.;Verdone, James E.;Pienta, Kenneth J.
通讯作者：
Pienta, Kenneth J.