腹水性自主磷酸酶磷化酶作为上皮性卵巢癌的潜在预后、诊断和治疗靶点。
Ascitic autotaxin as a potential prognostic, diagnostic, and therapeutic target for epithelial ovarian cancer.
发表日期:2023 Aug 18
作者:
Jung-A Choi, Hyosun Kim, Hyunja Kwon, Elizabeth Hyeji Lee, Hanbyoul Cho, Joon-Yong Chung, Jae-Hoon Kim
来源:
BRITISH JOURNAL OF CANCER
摘要:
恶性腹水通过促进卵巢肿瘤细胞在腹膜表面的多发性播散,对转移过程起到了一定的贡献。然而,腹水液的预后和诊断价值大多仍然未知。本研究旨在探讨腹水自体T凄凉酸酯酶(ATX)在上皮性卵巢癌(EOC)中的潜在临床价值和治疗效果。我们对临床样本中的ATX表达进行了评估。通过球体形成实验、实时荧光定量PCR、蛋白质印迹分析、侵袭块试验和黏附试验等方法加以了解。与良性腹水相比,卵巢癌患者的腹水中ATX表达显著增高,并与晚期、高分级以及病程短的EOC患者相关。将腹水中ATX与血清CA-125水平的诊断能力相结合,显著提高了EOC的曲线下面积(AUC)值,比单独血清CA-125水平更具诊断意义。这种标志物组合在高危EOC组中显示了较大的短病程的比值比。功能研究显示,腹水中的ATX对于维持肿瘤干细胞样特性和侵袭块形成具有必要性。腹水中ATX水平可能作为预测EOC侵袭行为的有用预后指标。ATX相关的侵袭块是预防卵巢癌腹膜播散的潜在治疗靶点。© 2023. 作者。
Malignant ascites contributes to the metastatic process by facilitating the multifocal dissemination of ovarian tumour cells onto the peritoneal surface. However, the prognostic and diagnostic relevance of ascitic fluid remains largely unknown. Herein, we investigated the potential clinical value and therapeutic utility of ascitic autotaxin (ATX) in epithelial ovarian cancer (EOC).ATX expression was assessed in clinical samples. Spheroid-forming assay, real-time PCR, western blot analysis, invadopodia assay, and adhesion assays were performed.Ascitic ATX expression was highly elevated in patients with ovarian cancer compared to those with benign ascites and was associated with advanced stage, high grade, and a short disease-free period in patients with EOC. Combining the diagnostic ability of ascitic ATX and serum CA-125 levels significantly improved the area under the curve (AUC) value for EOC compared to serum CA125 level alone. This marker combination showed a large odds ratio for short disease-free period in high-risk EOC groups. Functional studies revealed that ascitic ATX was required for maintaining cancer stem cell-like characteristics and invadopodia formation.Ascitic ATX levels may serve as a useful prognostic indicator for predicting aggressive behaviour in EOC. ATX-linked invadopodia are a potential target to prevent peritoneal dissemination in ovarian cancer.© 2023. The Author(s).