Pôle de Recherche en Gynécologie, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Avenue Mounier 52, B1.52.02, 1200 Brussels, Belgium.
Société de Recherche pour l Infertilité SRI, Avenue Grandchamp 143, 1150 Brussels, Belgium.
Reprod Biomed Online. 2018 Aug;37(2):224-233. doi: 10.1016/j.rbmo.2018.04.050. Epub 2018 May 7.
Does ulipristal acetate (UPA) modify the expression of genes related to apoptosis or the extracellular matrix in uterine myomas and are any modifications associated with a clinical response?
Targeted analysis of 176 apoptosis- or extracellular-matrix-related genes was conducted using polymerase chain reaction (PCR) arrays. Relevant results were validated by quantitative PCR. Four groups were established: responsive short-term (one course, n = 9), responsive long-term (two to four courses, n = 9), non-responsive (n = 9), and the control group who was not given any hormone therapy (n = 9). The clinical response was monitored by medical imagery and considered significant when volume reduction was greater than 25%.
Compared with untreated myomas, significant changes in expression of four genes were found in UPA-treated myomas. Gene expression of integrin subunit beta 4 was repressed by UPA treatment (fold change [FC] = -12.50, P < 0.001, q < 0.001), tenascin-C expression was downregulated in UPA-responsive patients (FC = -2.50, P = 0.010, q = 0.090), survivin was repressed in short-term UPA-responsive tumours (FC = -7.69, P < 0.001, q = 0.010), and catenin delta 2 gene expression was upregulated in non-responsive myomas (FC = +7.36, P < 0.001, q = 0.010).
This characterization provides the first molecular distinction between myomas responsive or non-responsive to UPA treatment.
屈螺酮（UPA）是否会改变子宫肌瘤中与细胞凋亡或细胞外基质相关的基因表达，以及任何改变是否与临床反应相关？
使用聚合酶链反应（PCR）阵列对 176 个与细胞凋亡或细胞外基质相关的基因进行靶向分析。通过定量 PCR 验证相关结果。建立了 4 个组：短期反应组（一个疗程，n = 9）、长期反应组（两个至四个疗程，n = 9）、无反应组（n = 9）和未接受任何激素治疗的对照组（n = 9）。通过医学影像学监测临床反应，当体积减少大于 25%时认为是显著的。
与未治疗的肌瘤相比，在 UPA 治疗的肌瘤中发现了四个基因表达的显著变化。整合素亚基β4 的基因表达被 UPA 治疗抑制（倍数变化[FC] = -12.50，P < 0.001，q < 0.001），在 UPA 反应性患者中，tenascin-C 的表达下调（FC = -2.50，P = 0.010，q = 0.090），在短期 UPA 反应性肿瘤中，survivin 的基因表达被抑制（FC = -7.69，P < 0.001，q = 0.010），在无反应性肌瘤中，catenin delta 2 的基因表达上调（FC = +7.36，P < 0.001，q = 0.010）。
这种特征分析首次提供了 UPA 治疗反应性或无反应性子宫肌瘤之间的分子区别。
