Osteikoetxea Xabier, Benke Márton, Rodriguez Marta, Pálóczi Krisztina, Sódar Barbara W, Szvicsek Zsuzsanna, Szabó-Taylor Katalin, Vukman Krisztina V, Kittel Ágnes, Wiener Zoltán, Vékey Károly, Harsányi László, Szűcs Ákos, Turiák Lilla, Buzás Edit I
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary; 1st Department of Surgery, Semmelweis University, Budapest, Hungary.
Biochem Biophys Res Commun. 2018 Apr 30;499(1):37-43. doi: 10.1016/j.bbrc.2018.03.107. Epub 2018 Mar 21.
The prognosis of patients with pancreatic cancer has remained virtually unchanged with a high mortality rate compared to other types of cancers. An earlier detection would provide a time window of opportunity for treatment and prevention of deaths. In the present study we investigated extracellular vesicle (EV)-associated potential biomarkers for pancreatic cancer by directly assessing EV size-based subpopulations in pancreatic juice samples of patients with chronic pancreatitis or pancreatic cancer. In addition, we also studied blood plasma and pancreatic cancer cell line-derived EVs.
Comparative proteomic analysis was performed of 102 EV preparations from human pancreatic juices, blood, and pancreatic cancer cell lines Capan-1 and MIA PaCa-2. EV preparations were also characterized by electron microscopy, tunable resistive pulse sensing, and flow cytometry.
Here we describe the presence of EVs in human pancreatic juice samples. Pancreatic juice EV-associated proteins that we identified as possible candidate markers for pancreatic cancer included mucins, such as MUC1, MUC4, MUC5AC, MUC6 and MUC16, CFTR, and MDR1 proteins. These candidate biomarkers could also be detected by flow cytometry in EVs found in pancreatic juice and those secreted by pancreatic cancer cell lines.
Together our data show that detection and characterization of EVs directly in pancreatic juice is feasible and may prove to be a valuable source of potential biomarkers of pancreatic cancer.
与其他类型癌症相比，胰腺癌患者的预后几乎没有变化，死亡率很高。早期检测可为治疗和预防死亡提供一个机会窗口。在本研究中，我们通过直接评估慢性胰腺炎或胰腺癌患者胰液样本中基于细胞外囊泡（EV）大小的亚群，研究了与胰腺癌相关的细胞外囊泡潜在生物标志物。此外，我们还研究了血浆和胰腺癌细胞系来源的细胞外囊泡。
对来自人胰液、血液以及胰腺癌细胞系Capan-1和MIA PaCa-2的102份细胞外囊泡制剂进行了比较蛋白质组学分析。细胞外囊泡制剂还通过电子显微镜、可调电阻脉冲传感和流式细胞术进行了表征。
在此我们描述了人胰液样本中细胞外囊泡的存在情况。我们鉴定出的与胰腺癌可能的候选标志物相关的胰液细胞外囊泡蛋白包括粘蛋白，如MUC1、MUC4、MUC5AC、MUC6和MUC16、囊性纤维化跨膜传导调节因子（CFTR）以及多药耐药蛋白1（MDR1）。这些候选生物标志物也可通过流式细胞术在胰液中发现的细胞外囊泡以及胰腺癌细胞系分泌的细胞外囊泡中检测到。
我们的数据共同表明，直接在胰液中检测和表征细胞外囊泡是可行的，并且可能被证明是胰腺癌潜在生物标志物的宝贵来源。
