Wu Wei, Yong Wen Wei, Chung Maxey C M
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore.
Proteomics. 2016 Nov;16(22):2921-2930. doi: 10.1002/pmic.201600194. Epub 2016 Sep 6.
Gastric cancer (GC) is a major cause of death in many parts of the world. While 90% of early GC is curable by resection, only about 5% of patients diagnosed in the late stages survive beyond five years. This provides strong impetus to push for early GC detection through the use of non-invasive biomarkers, before metastatic complications arise. It is also of strong medical interest to identify patients of the diffuse subtype at the earliest time possible, since the disease variant progresses very rapidly and is associated with much higher mortality rate. In this study, we compared quantitatively the gastric fluid proteome of 70 GC patients to 17 individuals with benign gastritis in search of potential biomarkers that aid in GC diagnosis, prognosis and subtype stratification. We report that as much as half of the gastric fluid proteome is subject to regulation in diseased states, and propose a simple biomarker panel scoring matrix for early GC detection with diagnostic sensitivity of 95.7%. We also demonstrate as proof-of-concept that a digitised record generated with SWATH-MS based on 380 protein abundance signatures from the gastric fluid could segregate patients with diffuse-type GC.
胃癌(GC)是世界许多地区的主要死因。虽然90%的早期胃癌可通过手术治愈,但在晚期确诊的患者中只有约5%能存活超过五年。这为在转移性并发症出现之前通过使用非侵入性生物标志物推动早期胃癌检测提供了强大动力。尽早识别弥漫性亚型患者也具有重要的医学意义,因为这种疾病变体进展非常迅速且死亡率高得多。在本研究中,我们对70例胃癌患者和17例慢性胃炎患者的胃液蛋白质组进行了定量比较,以寻找有助于胃癌诊断、预后和亚型分层的潜在生物标志物。我们报告称,多达一半的胃液蛋白质组在疾病状态下受到调控,并提出了一种简单的生物标志物面板评分矩阵用于早期胃癌检测,诊断敏感性为95.7%。我们还作为概念验证证明,基于来自胃液的380个蛋白质丰度特征通过SWATH-MS生成的数字化记录可以区分弥漫型胃癌患者。