Taleb Raghda Saad Zaghloul, Moez Pacint, Younan Doreen, Eisenacher Martin, Tenbusch Matthias, Sitek Barbara, Bracht Thilo
Medizinisches Proteom-Center, Ruhr-Universität Bochum, Bochum, Germany.
Clinical and Chemical Pathology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Proteomics Clin Appl. 2017 Dec;11(11-12). doi: 10.1002/prca.201700014. Epub 2017 Jul 10.
Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and a leading cause of cancer-related deaths worldwide. Cirrhosis induced by hepatitis-C virus (HCV) infection is the most critical risk factor for HCC. However, the mechanism of HCV-induced carcinogenesis is not fully understood. Plasma microparticles (PMP) contribute to numerous physiological and pathological processes and contain proteins whose composition correlates to the respective pathophysiological conditions.
We analyzed PMP from 22 HCV-induced cirrhosis patients, 16 HCV-positive HCC patients with underlying cirrhosis and 18 healthy controls. PMP were isolated using ultracentrifugation and analyzed via label-free LC-MS/MS.
We identified 840 protein groups and quantified 507 proteins. 159 proteins were found differentially abundant between the three experimental groups. PMP in both disease entities displayed remarkable differences in the proteome composition compared to healthy controls. Conversely, the proteome difference between both diseases was minimal. GO analysis revealed that PMP isolated from both diseases were significantly enriched in proteins involved in complement activation, while endopeptidase activity was downregulated exclusively in HCC patients.
This study reports for the first time a quantitative proteome analysis for PMP from patients with HCV-induced cirrhosis and HCC. Data are available via ProteomeXchange with identifier PXD005777.
肝细胞癌（HCC）是最常见的原发性肝脏恶性肿瘤，也是全球癌症相关死亡的主要原因。丙型肝炎病毒（HCV）感染所致肝硬化是HCC最关键的危险因素。然而，HCV诱导致癌的机制尚未完全阐明。血浆微粒（PMP）参与众多生理和病理过程，其所含蛋白质的组成与各自的病理生理状况相关。
我们分析了22例HCV诱导肝硬化患者、16例伴有潜在肝硬化的HCV阳性HCC患者以及18例健康对照者的PMP。采用超速离心法分离PMP，并通过无标记液相色谱 - 串联质谱法进行分析。
我们鉴定出840个蛋白组，定量了507种蛋白质。在三个实验组之间发现159种蛋白质丰度存在差异。与健康对照相比，两种疾病实体中的PMP在蛋白质组组成上均表现出显著差异。相反，两种疾病之间的蛋白质组差异最小。基因本体（GO）分析显示，从两种疾病中分离出的PMP在参与补体激活的蛋白质中显著富集，而内肽酶活性仅在HCC患者中下调。
本研究首次报道了对HCV诱导肝硬化和HCC患者PMP的定量蛋白质组分析。数据可通过ProteomeXchange获得，标识符为PXD005777。
