Leucine-rich alpha-2-glycoprotein-1 is upregulated in sera and tumors of ovarian cancer patients.
Leucine-rich alpha-2-glycoprotein-1 is upregulated in sera and tumors of ovarian cancer patients.
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DOI：
10.1186/1757-2215-3-21
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发表时间：
2010-09-10
影响因子：
4
通讯作者：
Skubitz AP
中科院分区：
文献类型：
--
作者：
Andersen JD;Boylan KL;Jemmerson R;Geller MA;Misemer B;Harrington KM;Weivoda S;Witthuhn BA;Argenta P;Vogel RI;Skubitz AP
需要新的生物标志物来替代或与目前的卵巢癌诊断抗原CA125一起使用，以在手术前环境中检测卵巢癌，以及检测疾病复发。我们先前使用定量质谱仪证实了卵巢癌患者血清中富含亮氨酸的α-2-糖蛋白-1(LRG1)的上调。用酶联免疫吸附试验测定了卵巢癌和良性妇科疾病两个相对较大的队列妇女血清中LRG1的含量。采用基因芯片、逆转录聚合酶链式反应、Western印迹、免疫细胞化学和质谱仪等方法检测LRG1在卵巢癌组织和细胞系中的表达。58例卵巢癌患者血清LRG1值(89.33±77.90ug/ml)明显高于56例健康妇女(42.99±9.88ug/ml；P=0.0008)，且以III/IV期患者最高。在一组单独的手术前样本中，浆液性或透明细胞卵巢癌患者的LRG1值(145.82±65.99ug/ml)高于良性妇科疾病患者(82.53ug/ml±76.67ug/ml，p<；0.0001)。CA125值与LRG1值呈中度相关(r=0.47p<；0.0001)。通过基因芯片和RT-PCR分析，卵巢癌组织和细胞系中LRG1mRNA的表达水平高于正常卵巢癌组织和细胞系。免疫细胞化学和Western blotting检测到LRG1蛋白在卵巢癌组织和细胞系中的表达。Western印迹显示LRG1有多种异构体，经糖苷酶消化后呈现不同的糖基化状态。用ELISA法、Western blotting法和质谱仪检测卵巢癌细胞条件培养液中LRG1蛋白的表达。与健康妇女和良性妇科疾病妇女相比，卵巢癌妇女的血清LRG1显著升高，且仅与CA125中等相关。卵巢癌细胞分泌LRG1，可能是卵巢癌患者血清中LRG1水平升高的直接原因。未来的研究将确定LRG1是否可以作为术前诊断、疾病复发和/或治疗目标的生物标记物。
New biomarkers that replace or are used in conjunction with the current ovarian cancer diagnostic antigen, CA125, are needed for detection of ovarian cancer in the presurgical setting, as well as for detection of disease recurrence. We previously demonstrated the upregulation of leucine-rich alpha-2-glycoprotein-1 (LRG1) in the sera of ovarian cancer patients compared to healthy women using quantitative mass spectrometry. LRG1 was quantified by ELISA in serum from two relatively large cohorts of women with ovarian cancer and benign gynecological disease. The expression of LRG1 in ovarian cancer tissues and cell lines was examined by gene microarray, reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot, immunocytochemistry and mass spectrometry. Mean serum LRG1 was higher in 58 ovarian cancer patients than in 56 healthy women (89.33 ± 77.90 vs. 42.99 ± 9.88 ug/ml; p = 0.0008) and was highest among stage III/IV patients. In a separate set of 193 pre-surgical samples, LRG1 was higher in patients with serous or clear cell ovarian cancer (145.82 ± 65.99 ug/ml) compared to patients with benign gynecological diseases (82.53 ± 76.67 ug/ml, p < 0.0001). CA125 and LRG1 levels were moderately correlated (r = 0.47, p < 0.0001). LRG1 mRNA levels were higher in ovarian cancer tissues and cell lines compared to their normal counterparts when analyzed by gene microarray and RT-PCR. LRG1 protein was detected in ovarian cancer tissue samples and cell lines by immunocytochemistry and Western blotting. Multiple iosforms of LRG1 were observed by Western blot and were shown to represent different glycosylation states by digestion with glycosidase. LRG1 protein was also detected in the conditioned media of ovarian cancer cell culture by ELISA, Western blotting, and mass spectrometry. Serum LRG1 was significantly elevated in women with ovarian cancer compared to healthy women and women with benign gynecological disease, and was only moderately correlated with CA125. Ovarian cancer cells secrete LRG1 and may contribute directly to the elevated levels of LRG1 observed in the serum of ovarian cancer patients. Future studies will determine whether LRG1 may serve as a biomarker for presurgical diagnosis, disease recurrence, and/or as a target for therapy.
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影响因子：
4.4
作者：
Gortzak-Uzan, Limor;Ignatchenko, Alex;Kislinger, Thomas
通讯作者：
Kislinger, Thomas
DOI：
10.1515/bchm2.1977.358.1.639
发表时间：
1977-01-01
影响因子：
--
作者：
HAUPT, H;BAUDNER, S
通讯作者：
BAUDNER, S
影响因子：
4
作者：
Casey, RC;Oegema, TR;Skubitz, APN
通讯作者：
Skubitz, APN
影响因子：
2.5
作者：
Li, Xianfeng;Miyajima, Masakazu;Arai, Hajime
通讯作者：
Arai, Hajime
影响因子：
5.5
作者：
Ai, Jing;Druhan, Lawrence J.;Avalos, Belinda R.
通讯作者：
Avalos, Belinda R.