Purpose

Endometriosis (EM) is a common gynecological disease affecting 10–15% of women of reproductive age. However, molecular mechanisms and pathogenesis are still not completely understood. Furthermore, due to the absence of a reliable clinical biomarker, the only viable method for the often-delayed definitive diagnosis is laparoscopic surgery. Our objective was to analyze molecular differences of selected endometrial proteins and genes of women suffering from different stages of EM compared with healthy women to evaluate potential clinical biomarkers.

Methods

We analyzed eutopic endometrial tissue samples from women undergoing a laparoscopic surgery (n = 58). mRNA gene expression of progranulin (GRN), neurogenic locus notch homolog protein (NOTCH3), fibronectin (FN1), and PTEN-induced kinase 1 (PINK1) was analyzed using qRT-PCR. Protein expression was determined using ELISA and immunohistochemistry.

Results

Significant differences in gene expression between the different stages of the disease were noted for GRN, NOTCH3, FN1, and PINK1 (p < 0.05). The endometrium of women with minimal EM (ASRM I) showed the highest mRNA expression. Protein levels of GRN and FN1 on the other hand were significantly decreased in the endometrium of women with EM compared with those of healthy controls. Furthermore, for GRN and FN1, we could detect a correlation of protein expression with the severity of the disease.

Conclusion

Our findings suggest a potential use of GRN and FN1 as clinical biomarkers to detect endometriosis. In addition, GRN, NOTCH3, FN1, and PINK1 could potentially be useful to differentiate between the underlying stages of the disease. However, a validation with a larger study population is needed.

中文翻译：

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在原位子宫内膜中的GRN，NOTCH3，FN1和PINK1表达–检测子宫内膜异位症的潜在生物标志物–一项初步研究

目的

子宫内膜异位症（EM）是一种常见的妇科疾病，影响了10-15％的育龄妇女。但是，分子机制和发病机理仍未完全了解。此外，由于缺乏可靠的临床生物标志物，通常延迟进行明确诊断的唯一可行方法是腹腔镜手术。我们的目的是分析与健康女性相比，处于不同EM阶段的女性子宫内膜蛋白质和基因的分子差异，以评估潜在的临床生物标志物。

方法

我们分析了接受腹腔镜手术的妇女的异位子宫内膜组织样本（n = 58）。使用qRT-PCR分析了前颗粒蛋白（GRN），神经源性基因缺口同源蛋白（NOTCH3），纤连蛋白（FN1）和PTEN诱导的激酶1（PINK1）的mRNA基因表达。使用ELISA和免疫组织化学确定蛋白质表达。

结果

对于GRN，NOTCH3，FN1和PINK1，注意到该疾病不同阶段之间基因表达的显着差异（p <0.05）。EM（ASRM I）最低的女性的子宫内膜显示出最高的mRNA表达。另一方面，与健康对照组相比，EM妇女的子宫内膜中GRN和FN1的蛋白质水平显着降低。此外，对于GRN和FN1，我们可以检测蛋白质表达与疾病严重程度的相关性。

结论

我们的发现表明，将GRN和FN1用作检测子宫内膜异位症的临床生物标记物的潜在用途。此外，GRN，NOTCH3，FN1和PINK1可能有助于区分疾病的潜在阶段。但是，需要更多的研究人群进行验证。