Extracellular vesicles (EVs), including exosomes and microvesicles, mediate intercellular communication in cancer, from development to metastasis. EV-based liquid biopsy is a promising strategy for cancer diagnosis as EVs can be found in cancer patients’ body fluids. In this study, the lipid composition of breast cancer-derived EVs was studied as well as the potential of blood plasma EVs for the identification of lipid biomarkers for breast cancer detection. Initially, an untargeted lipidomic analysis was carried out for a panel of cancerous and non-cancerous mammary epithelial cells and their secreted EVs. We found that breast cancer-derived EVs are enriched in sphingolipids and glycerophospholipids compared to their parental cells. The initial in vitro study showed that EVs and their parental cells can be correctly classified (100% accuracy) between cancerous and non-cancerous, as well as into their respective breast cancer subtypes, based on their lipid composition. Subsequently, an untargeted lipidomic analysis was carried out for blood plasma EVs from women diagnosed with breast cancer (primary or progressive metastatic breast cancer) as well as healthy women. Correspondingly, when blood plasma EVs were analysed, breast cancer patients and healthy women were correctly classified with an overall accuracy of 93.1%, based on the EVs’ lipid composition. Similarly, the analysis of patients with primary breast cancer and healthy women showed an overall accuracy of 95% for their correct classification. Furthermore, primary and metastatic breast cancers were correctly classified with an overall accuracy of 89.5%. This reveals that the blood plasma EVs’ lipids may be a promising source of biomarkers for detection of breast cancer. Additionally, this study demonstrates the usefulness of untargeted lipidomics in the study of EV lipid composition and EV-associated biomarker discovery studies. This is a proof-of-concept study and a starting point for further analysis on the identification of EV-based biomarkers for breast cancer.

中文翻译：

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细胞外囊泡作为血浆中乳腺癌检测的脂质生物标志物的有前途的来源

细胞外囊泡（EV），包括外泌体和微泡，介导癌症从发育到转移的细胞间通讯。基于 EV 的液体活检是一种有前途的癌症诊断策略，因为可以在癌症患者的体液中发现 EV。在这项研究中，研究了乳腺癌来源的 EV 的脂质组成以及血浆 EV 在鉴定乳腺癌检测脂质生物标志物方面的潜力。最初，对一组癌性和非癌性乳腺上皮细胞及其分泌的 EV 进行了非靶向脂质组学分析。我们发现，与亲本细胞相比，乳腺癌来源的 EV 富含鞘脂和甘油磷脂。最初的体外研究表明，EV 及其亲代细胞可以根据其脂质成分正确分类（100% 准确度）癌性和非癌性，以及各自的乳腺癌亚型。随后，对诊断为乳腺癌（原发性或进行性转移性乳腺癌）的女性以及健康女性的血浆 EV 进行了非靶向脂质组学分析。相应地，在分析血浆 EV 时，根据 EV 的脂质成分，对乳腺癌患者和健康女性进行了正确分类，总体准确率为 93.1%。同样，对原发性乳腺癌患者和健康女性的分析显示，其正确分类的总体准确率为 95%。此外，原发性乳腺癌和转移性乳腺癌被正确分类，总体准确率为 89.5%。这表明血浆 EV 的脂质可能是检测乳腺癌的生物标志物的有前途的来源。此外，本研究证明了非靶向脂质组学在 EV 脂质成分研究和 EV 相关生物标志物发现研究中的有用性。这是一项概念验证研究，也是进一步分析基于 EV 的乳腺癌生物标志物鉴定的起点。