Glucose-Regulated Protein 78 Is a Potential Serum and Imaging Marker for Early Detection of Ovarian Cancer.
Glucose-Regulated Protein 78 Is a Potential Serum and Imaging Marker for Early Detection of Ovarian Cancer.
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葡萄糖调节的蛋白78是一种潜在的血清和成像标记，用于早期检测卵巢癌。
作者：
卵巢癌（OVCA）是一种致命的妇科疾病，目前尚无早期检测方法。葡萄糖调节蛋白 78 (GRP78) 是压力的蛋白质标志物，在慢性压力期间会增加。慢性压力被认为是癌症发展的标志。本研究探讨了GRP78的表达是否与OVCA的发生有关以及GRP78是否可以在早期预测OVCA。这项研究发现，在 OVCA 发育和进展过程中，GRP78 的表达及其在血液中的分泌增加。这项研究还开发了一种针对 GRP78 的超声扫描剂，可以在早期检测卵巢肿瘤。因此，血液中 GRP78 水平较高的女性可能需要进行靶向超声扫描，以确认她是否患有卵巢肿瘤。这些结果将为临床研究奠定基础，以检验 GRP78 作为血液和超声扫描早期检测 OVCA 的潜在标志物的可行性。背景：了解与卵巢癌（OVCA）相关的恶性转化对于建立早期检测测试非常重要。本研究检验了 OVCA 发育过程中葡萄糖调节蛋白 78（GRP78，细胞应激标志物）的表达是否增加，以及 GRP78 是否可以通过靶向经阴道超声 (TVUS) 成像检测到。方法：通过免疫组织化学、免疫印迹、基因表达和免疫测定法，检测正常卵巢（n = 10）、早期良性卵巢肿瘤（n = 10）和恶性卵巢肿瘤（n = 8）和晚期卵巢肿瘤（n = 16）、早期和晚期患有和不患有卵巢肿瘤的母鸡（n = 10，各10只）在OVCA发育过程中的GRP78表达。检查了 GRP78 靶向 TVUS 成像检测早期 OVCA 的可行性。结果：与正常卵巢和良性肿瘤相比，OVCA 患者 GRP78 表达强度较高（p < 0.0001）。与正常人 (9007.76 ± 816.54 pg/mL) 相比，早期 (12,730.59 ± 817.35 pg/mL) 和晚期 OVCA 患者 (13,930.12 ± 202.35) 血清 GRP78 水平显着升高 (p < 0.05) (p < 0.01)。与正常值 (222.62 ± 181.69 pg/mL) 相比，早期 (590.19 ± 198.18 pg/mL) 和晚期 OVCA (1261.38 ± 372.85) 的母鸡血清 GRP78 水平升高 (p < 0.05) (p < 0.01)。与非靶向相比，GRP78 靶向成像增强了 TVUS 的信号强度 (p < 0.0001)。结论：组织和血清中 GRP78 水平的升高与 OVCA 相关。 GRP78 为早期 OVCA 检测提供了潜在的血清和成像标记物。
Ovarian cancer (OVCA) is a fatal gynecological disease for which there is no early detection test. Glucose-regulated protein 78 (GRP78), a protein marker of stress, increases during chronic stress. Chronic stress has been suggested as a hallmark of cancer development. This study examined whether expression of GRP78 is associated with development of OVCA and whether GRP78 can predict OVCA at early stage. This study found GRP78 expression and its secretion in blood increased during OVCA development and progression. This study also developed a GRP78-targeted ultrasound scanning agent that detected ovarian tumors at early stages. Thus, a woman with high levels of GRP78 in her blood may be referred to have targeted-ultrasound scanning for confirming if she has ovarian tumors. These results will be a foundation for a clinical study to examine the feasibility of GRP78 as a potential marker of blood and ultrasound scanning for early detection of OVCA. Background: Understanding malignant transformation associated with ovarian cancer (OVCA) is important to establish early detection tests. This study examined whether expression of glucose-regulated protein 78 (GRP78, marker of cellular stress) increases during OVCA development, and whether GRP78 can be detected by targeted-transvaginal ultrasound (TVUS) imaging. Methods: Normal ovaries (n = 10), benign (n = 10) and malignant ovarian tumors at early (n = 8) and late stages (n = 16), hens with and without ovarian tumors at early and late stages (n = 10, each) were examined for GRP78 expression during OVCA development by immunohistochemistry, immunoblotting, gene expression and immunoassay. Feasibility of GRP78-targeted TVUS imaging in detecting early OVCA was examined. Results: Compared with normal ovaries and benign tumors, intensity of GRP78 expression was higher (p < 0.0001) in OVCA patients. Compared with normal (9007.76 ± 816.54 pg/mL), serum GRP78 levels were significantly higher (p < 0.05) in patients with early (12,730.59 ± 817.35 pg/mL) and late-stage OVCA (13,930.12 ± 202.35) (p < 0.01). Compared with normal (222.62 ± 181.69 pg/mL), serum GRP78 levels increased (p < 0.05) in hens with early (590.19 ± 198.18 pg/mL) and late-stage OVCA (1261.38 ± 372.85) (p < 0.01). Compared with non-targeted, GRP78-targeted imaging enhanced signal intensity of TVUS (p < 0.0001). Conclusions: Tissue and serum levels of GRP78 increase in association with OVCA. GRP78 offers a potential serum and imaging marker for early OVCA detection.
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实现癌症基因组数据的共同愿景。
DOI：
10.1056/nejmp1607591
发表时间：
2016-09-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Grossman RL;Heath AP;Ferretti V;Varmus HE;Lowy DR;Kibbe WA;Staudt LM
通讯作者：
Staudt LM
影响因子：
--
作者：
Calaf GM;Urzua U;Termini L;Aguayo F
通讯作者：
Aguayo F
影响因子：
4.4
作者：
Elssner, A;Doseff, AI;Wewers, MD
通讯作者：
Wewers, MD
影响因子：
4.8
作者：
Barker, S;Weinfeld, M;Murray, D
通讯作者：
Murray, D
影响因子：
2.3
作者：
Barua, Animesh;Abramowicz, Jacques S.;Luborsky, Judith L.
通讯作者：
Luborsky, Judith L.