Small extracellular vesicles (sEVs) contain lipids, proteins and nucleic acids, which often resemble their cells of origin. Therefore, plasma sEVs are considered valuable resources for cancer biomarker development. However, previous efforts have been largely focused on the level of proteins and miRNAs in plasma sEVs, and the post-translational modifications of sEV proteins, such as arginine methylation, have not been explored. Protein arginine methylation, a relatively stable post-translational modification, is a newly described molecular feature of PDAC. The present study examined arginine methylation patterns in plasma sEVs derived from patients with early-stage PDAC (n= 23) and matched controls. By utilizing the arginine methylation-specific antibodies for western blotting, we found that protein arginine methylation patterns in plasma sEVs are altered in patients with early-stage PDAC. Specifically, we observed a reduction in the level of symmetric dimethyl arginine (SDMA) in plasma sEV proteins derived from patients with early- and late-stage PDAC. Importantly, immunoprecipitation followed by proteomics analysis identified a number of arginine-methylated proteins exclusively present in plasma sEVs derived from patients with early-stage PDAC. These results indicate that arginine methylation patterns in plasma sEVs are potential indicators of PDAC, a new concept meriting further investigation.
小细胞外囊泡（sEVs）含有脂质、蛋白质和核酸，其成分通常与来源细胞相似。因此，血浆sEVs被视为癌症生物标志物开发的重要资源。然而，既往研究主要集中于血浆sEVs中蛋白质和微小核糖核酸的水平，尚未深入探索sEVs蛋白质的翻译后修饰，如精氨酸甲基化。蛋白质精氨酸甲基化作为一种相对稳定的翻译后修饰，是胰腺导管腺癌（PDAC）新近发现的分子特征。本研究检测了早期PDAC患者（n=23）与匹配对照组血浆来源sEVs的精氨酸甲基化模式。通过使用精氨酸甲基化特异性抗体进行蛋白质印迹分析，我们发现早期PDAC患者血浆sEVs中的蛋白质精氨酸甲基化模式发生改变。具体而言，我们观察到早期和晚期PDAC患者血浆sEVs蛋白质中对称二甲基精氨酸（SDMA）水平降低。重要的是，通过免疫沉淀结合蛋白质组学分析，鉴定出仅在早期PDAC患者血浆sEVs中存在的多种精氨酸甲基化蛋白质。这些结果表明，血浆sEVs中的精氨酸甲基化模式是PDAC的潜在指标，这一新概念值得进一步研究。
肿瘤(癌症)患者之家