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【科技前瞻】ACS Nano:外泌体蛋白质标志物分析能够快速检测胰腺癌

上海市脐带血造血干细胞库 2019-03-14 11:41:39

有报道指出,预计到2020年,胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)将成为美国癌症死亡的第二大原因。PDAC常见的症状是非特异性的体重减轻和上腹部疼痛,容易造成误诊。其诊断目前主要依赖成像方法,如增强计算机断层扫描(CT)、磁共振成像(MRI)和内镜超声,然后通过肿瘤组织活检进行确认。要想在PDAC进展之前进行诊断,就要依赖于液体活检新技术,但现有的肿瘤生物标志物,如CA19-9和癌胚抗原CEA等,既不敏感也不足以作为有效的早期诊断检测方式。目前,磷脂酰肌醇蛋白聚糖-1(Glypican-1)被确定为胰腺癌有潜在价值的外泌体生物标志物。

外泌体是小的纳米级实体,能从健康细胞和癌细胞中释放,进入血液和其他体液,同时携带蛋白质和核酸生物标志物。由于它们反映了原始细胞的基因型和表型,因此可以在没有肿瘤组织活检的情况下针对癌症或其他疾病进行筛选。但由于其体积非常小且密度低,因此分离十分困难。此前,已有研究提出使用交流电动力学(alternating current electrokinetic,ACE)微阵列芯片装置能在15-20分钟内直接从全血、血浆或血清中分离成胶质细胞瘤外泌体和其他纳米级实体,同时可以在90分钟内在未稀释的胰腺癌患者全血、血浆或血清中检测到Glypican-1和CD63,不需要稀释或添加其他样品,如抗体、亲和珠或脂质。近日,研究人员使用ACE微阵列芯片,实现了在20分钟内从25μL未稀释的胰腺癌患者全血、血清或血浆中分离出外泌体和其他纳米级的物质(EV和cfDNA)。然后直接在芯片上进行生物标志物Glypican-1和CD63的集成免疫荧光标记和分析。定量荧光标记的生物标志物可以将PDAC患者样品集合(n =20)与来自健康个体和来自患有良性胰腺疾病或结肠癌患者的样品进行比较。结果成功区分PDAC患者与健康个体。此外,在部分结肠癌患者中进行实验时,该检测能够鉴定其中三种具有转移性的样品。

该研究表明,基于ACE微阵列芯片检测方法,能够快速准确地对胰腺癌进行早期诊断,表明外泌体作为胰腺癌或其他癌症的强大诊断工具得到了进一步发展。

 


推荐阅读原文:
Integrated Analysis of Exosomal Protein Biomarkers on Alternating Current Electrokinetic Chips Enables Rapid Detection of Pancreatic Cancer in Patient Blood.

Pancreatic ductal adenocarcinoma (PDAC) typically has nonspecific symptoms and is often found too late to treat. Because diagnosis of PDAC involves complex, invasive, and expensive procedures, screening populations at increased risk will depend on developing rapid, sensitive, specific, and cost-effective tests. Exosomes, which are nanoscale vesicles shed into blood from tumors, have come into focus as valuable entities for noninvasive liquid biopsy diagnostics. However, rapid capture and analysis of exosomes with their protein and other biomarkers have proven difficult. Here, we present a simple method integrating capture and analysis of exosomes and other extracellular vesicles directly from whole blood, plasma, or serum onto an AC electrokinetic microarray chip. In this process, no pretreatment or dilution of sample is required, nor is it necessary to use capture antibodies or other affinity techniques. Subsequent on-chip immunofluorescence analysis permits specific identification and quantification of target biomarkers within as little as 30 min total time. In this initial validation study, the biomarkers glypican-1 and CD63 were found to reflect the presence of PDAC and thus were used to develop a bivariate model for detecting PDAC. Twenty PDAC patient samples could be distinguished from 11 healthy subjects with 99% sensitivity and 82% specificity. In a smaller group of colon cancer patient samples, elevated glypican-1 was observed for metastatic but not for nonmetastatic disease. The speed and simplicity of ACE exosome capture and on-chip biomarker detection, combined with the ability to use whole blood, will enable seamless "sample-to-answer" liquid biopsy screening and improve early stage cancer diagnostics.




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