State Key Laboratory of Molecular Oncology, Beijing Key Laboratory for Carcinogenesis and Cancer Prevention, Cancer Institute (Hospital), Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100021, China.
Sci China Life Sci. 2013 Jul;56(7):638-46. doi: 10.1007/s11427-013-4497-x. Epub 2013 Jun 8.
For successful therapy, hepatocellular carcinoma (HCC) must be detected at an early stage. Herein, we used a proteomic approach to analyze the secretory/releasing proteome of HCC tissues to identify plasma biomarkers. Serum-free conditioned media (CM) were collected from primary cultures of cancerous tissues and surrounding noncancerous tissues. Proteomic analysis of the CM proteins permitted the identification of 1365 proteins. The enriched molecular functions and biological processes of the CM proteins, such as hydrolase activity and catabolic processes, were consistent with the liver being the most important metabolic organ. Moreover, 19% of the proteins were characterized as extracellular or membrane-bound. For validation, secretory proteins involved in transforming growth factor-β signaling pathways were validated in plasma samples. Alphafetoprotein (AFP), metalloproteinase (MMP)1, osteopontin (OPN), and pregnancy-specific beta-1-glycoprotein (PSG)9 were significantly increased in HCC patients. The overall performance of MMP1 and OPN in the diagnosis of HCC remained greater than that of AFP. In addition, this study represents the first report of MMP1 as a biomarker with a higher sensitivity and specificity than AFP. Thus, this study provides a valuable resource of the HCC secretome with the potential to investigate serological biomarkers. MMP1 and OPN could be used as novel biomarkers for the early detection of HCC and to improve the sensitivity of biomarkers compared with AFP.
为了成功治疗，肝癌 (HCC) 必须在早期被发现。在这里，我们使用蛋白质组学方法来分析 HCC 组织的分泌/释放蛋白质组，以鉴定血浆生物标志物。从癌症组织和周围非癌组织的原代培养物中收集无血清条件培养基 (CM)。CM 蛋白的蛋白质组学分析允许鉴定 1365 种蛋白质。CM 蛋白中富集的分子功能和生物过程，如水解酶活性和分解代谢过程，与肝脏是最重要的代谢器官一致。此外，19%的蛋白质被描述为细胞外或膜结合蛋白。为了验证，在血浆样本中验证了参与转化生长因子-β信号通路的分泌蛋白。甲胎蛋白 (AFP)、金属蛋白酶 (MMP)1、骨桥蛋白 (OPN) 和妊娠特异性β-1-糖蛋白 (PSG)9 在 HCC 患者中显著增加。MMP1 和 OPN 在 HCC 诊断中的整体性能仍然大于 AFP。此外，这项研究首次报道 MMP1 作为一种比 AFP 具有更高灵敏度和特异性的生物标志物。因此，本研究为 HCC 分泌组提供了有价值的资源，具有研究血清生物标志物的潜力。MMP1 和 OPN 可作为 HCC 早期检测的新型生物标志物，与 AFP 相比提高了生物标志物的灵敏度。
