Abstract：
Ovarian cancer (OC) is one of the most common and fatal types of gynecological cancer. In the early phase of OC detection, the current treatment and diagnostic methods are not efficient and sensitive enough. Therefore, it is crucial to explore the mechanisms of OC metastasis and discover valuable factors for early diagnosis of female cancers and novel therapeutic strategies for metastasis. Exosomes are known to be involved in the development, migration, and invasion of cancer cells, and their cargo could be useful for the non-invasive biopsy development. CD151- and Tspan8-positive exosomes are known to support the degradation of the extracellular matrix, and are involved in stroma remodeling, angiogenesis and cell motility, as well as the association of miR-24 and miR-101 with these processes. The objective of this study was to explore the relationship of these components of exosomal cargo, in patients with OC, to clarify the clinical significance of these markers in liquid biopsies. The levels of tetraspanins Tspan8+ and CD151+ exosomes were significantly higher in plasma exosomes of OC patients compared with healthy females (HFs). The relative levels of miR-24 and miR-101 in plasma exosomes of HFs were significantly higher than in plasma exosomes of OC patients, while the levels of these microRNAs in exosomes from plasma and ascites of ill females showed no difference. Our study revealed a strong direct correlation between the change in the ascites exosomes CD151+Tspan8+ subpopulation level and the expression levels of the ascites (R = 0.81, p < 0.05) and plasma exosomal miR-24 (R = 0.74, p < 0.05) in OC patients, which confirms the assumption that exosomal cargo act synergistically to increase cellular motility, affecting cellular processes and signaling. Bioinformatics analysis confirmed the involvement of CD151 and Tspan8 tetraspanins and genes controlled by miR-24-3p and miR-101 in signaling pathways, which are crucial for carcinogenesis, demonstrating that these tetraspanins and microRNAs are potential biomarkers for OC screening, and predictors of poor clinicopathological behavior in tumors.
摘要：
卵巢癌（OC）是妇科最常见和最致命的癌症之一。在OC检测的早期阶段，目前的治疗和诊断方法不够有效和灵敏。因此,探索OC转移的机制，发现有价值的因素对女性癌症的早期诊断和新的转移治疗策略至关重要。已知外泌体参与发育，迁移,和癌细胞的入侵，和他们的货物可能是有用的非侵入性活检的发展。已知CD151和Tspan8阳性外泌体支持细胞外基质的降解，参与基质重塑，血管生成和细胞运动，以及miR-24和miR-101与这些过程的关联。这项研究的目的是探讨外泌体货物的这些成分之间的关系，在OC患者中，阐明这些标志物在液体活检中的临床意义。与健康女性（HFs）相比，OC患者的血浆外泌体中的四跨膜蛋白Tspan8和CD151外泌体的水平显着升高。血浆外泌体中miR-24和miR-101的相对水平显著高于OC患者血浆外泌体,而这些microRNA在来自患病女性的血浆和腹水的外泌体中的水平没有差异。我们的研究揭示了腹水外泌体CD151Tspan8亚群水平的变化与腹水（R=0.81，p＆lt;0.05）和血浆外泌体miR-24（R=0.74，p＆lt;0.05）在OC患者中的表达水平之间存在很强的直接相关性，这证实了外泌体货物协同作用以增加细胞运动性的假设，影响细胞过程和信号。生物信息学分析证实了CD151和Tspan8四跨膜蛋白以及miR-24-3p和miR-101控制的基因参与信号通路,这对致癌作用至关重要，证明这些四跨膜蛋白和microRNAs是OC筛选的潜在生物标志物，以及肿瘤临床病理行为不良的预测因素。
