Novel Serum Biomarkers Detected by Protein Array in Polycystic Ovary Syndrome with Low Progesterone Level
Novel Serum Biomarkers Detected by Protein Array in Polycystic Ovary Syndrome with Low Progesterone Level
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通过蛋白质阵列检测低孕酮水平多囊卵巢综合征的新型血清生物标志物
DOI：
10.1159/000489619
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Yan, Qiu
中科院分区：
文献类型：
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作者：
Zheng, Qin;Zhou, Feifei;Yan, Qiu
背景/目标：多囊卵巢综合征（PCOS）是一种常见的内分泌疾病，以女性不孕和代谢异常为特征。PCOS的病因仍不清楚。综合分析PCOS患者的蛋白质改变对筛选PCOS的诊断标志物具有重要意义。在此，我们探讨了血清蛋白作为检测低孕酮水平PCOS的新生物标志物的临床价值。方法：选取43例PCOS患者和30例健康女性作为研究对象。采用蛋白质芯片技术检测PCOS患者与健康妇女血清蛋白质的差异。ELISA和western blot进一步证实了5种血清蛋白的水平。本研究通过体外培养人卵巢颗粒细胞（KGN）来探讨PCOS的发病机制。CCK 8法和western blot法检测KGN细胞增殖能力的变化，TUNEL法和DAPI染色检测KGN细胞凋亡。结果：在507个蛋白质中，我们鉴定出76个差异表达的蛋白质（1.5倍），其中40个升高，36个降低。此外，47个蛋白质是PCOS的新报告。ELISA和western blot进一步证实了EREG、βA、IDE、PDGF-D和KNG 1这5种蛋白质的改变。这些蛋白的表达水平与低孕酮水平直接相关，孕酮可上调其表达。EREG和Ereb in βA也能促进卵巢颗粒细胞增殖，抑制其凋亡。结论：该研究强调了PCOS患者和健康女性血清蛋白质的差异表达，孕酮上调EREG和Erebin βA水平，这与卵巢功能相关。提示EREG和βA有可能成为低孕酮PCOS的潜在生物标志物。
Background/Aims: Polycystic ovary syndrome (PCOS), characterized by female infertility and metabolic abnormalities, is one of the most common endocrine disorders. The etiology of PCOS remains unknown. The comprehensive analysis of protein alterations in PCOS patients is meaningful for identifying diagnostic biomarkers of PCOS. Here, we explored the clinical value of serum proteins as novel biomarkers to detect PCOS with low progesterone level. Methods: A total of 43 patients with PCOS and 30 healthy women were enrolled. Protein array was used to detect the variations of serum proteins between PCOS patients and healthy women. The level of five serum proteins was further confirmed by ELISA and western blot. The human ovarian granulosa cells (KGN) was cultured to examine the underlying mechanism of PCOS. CCK8 assay and western blot were carried out to evaluate the alterations in proliferative ability, TUNEL assay and DAPI staining to detect the apoptosis of KGN cells. Results: Among the 507 proteins, we identified 76 differentially expressed serum proteins (≧1.5 fold), with 40 elevated and 36 decreased proteins. Moreover, 47 proteins were newly reported in PCOS. The alterations in the five significantly decreased proteins (EREG, inhibin βA, IDE, PDGF-D and KNG1) were further confirmed by ELISA and western blot. The level of these proteins were directly associated with the low progesterone, and the expression could be upregulated by progesterone. EREG and inhibin βA also promoted the proliferation and inhibited the apoptosis of ovarian granulosa cells. Conclusion: The study highlights that serum proteins are differentially expressed in PCOS patients and healthy women, and EREG and inhibin βA levels are upregulated by progesterone, which are correlated with ovarian functions. The study suggests that EREG and inhibin βA may be applied as novel potential biomarkers for PCOS with low progesterone level.