Screening of Potential Biomarkers for Gastric Cancer with Diagnostic Value Using Label-free Global Proteome Analysis.
Screening of Potential Biomarkers for Gastric Cancer with Diagnostic Value Using Label-free Global Proteome Analysis.
复制标题
使用无标记全局蛋白质组分析筛选具有诊断价值的胃癌潜在生物标志物
DOI：
10.1016/j.gpb.2020.06.012
复制
发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Song Y;Wang J;Sun J;Chen X;Shi J;Wu Z;Yu D;Zhang F;Wang Z
胃癌（GC）是全球著名的恶性肿瘤类型之一。尽管近期死亡率有所下降，但其预后仍然不佳。因此，有必要寻找对胃癌具有早期诊断价值的新型生物标志物。在本研究中，我们利用无标记的全局蛋白质组分析技术，对30例胃癌组织和30例匹配的健康组织进行了大规模蛋白质组分析。我们的研究结果确定了537种差异表达的蛋白质，其中包括280种上调蛋白质和257种下调蛋白质。 Ingenuity通路分析（IPA）结果表明，去乙酰化酶（sirtuin）信号通路在胃癌组织中是最活跃的通路，而氧化磷酸化是最受抑制的通路。此外，最活跃的分子功能是细胞运动，包括肿瘤细胞系的组织侵袭。基于IPA结果，筛选出了15种关键蛋白。利用受试者工作特征曲线，大多数关键蛋白在区分肿瘤和健康对照方面显示出较高的诊断能力。利用随机森林模型构建了一个由四种蛋白质（ATP5B - ATP5O - NDUFB4 - NDUFB8）组成的诊断特征。该模型在训练集和测试集的曲线下面积（AUC）值分别为0.996和0.886，这表明四种蛋白质组成的诊断特征具有较高的诊断能力。利用血浆酶联免疫吸附测定法对独立数据集进一步测试该诊断特征，区分胃癌组织和健康对照的AUC值为0.778，利用免疫组织化学组织微阵列分析，AUC值为0.805。总之，本研究确定了潜在的生物标志物，增进了我们对发病机制的理解，为胃癌提供了新的治疗靶点。
Gastric cancer (GC) is known as a top malignant type of tumors worldwide. Despite the recent decrease in mortality rates, the prognosis remains poor. Therefore, it is necessary to find novel biomarkers with early diagnostic value for GC. In this study, we present a large-scale proteomic analysis of 30 GC tissues and 30 matched healthy tissues using label-free global proteome profiling. Our results identified 537 differentially expressed proteins, including 280 upregulated and 257 downregulated proteins. The ingenuity pathway analysis (IPA) results indicated that the sirtuin signaling pathway was the most activated pathway in GC tissues whereas oxidative phosphorylation was the most inhibited. Moreover, the most activated molecular function was cellular movement, including tissue invasion by tumor cell lines. Based on IPA results, 15 hub proteins were screened. Using the receiver operating characteristic curve, most of hub proteins showed a high diagnostic power in distinguishing between tumors and healthy controls. A four-protein (ATP5B-ATP5O-NDUFB4-NDUFB8) diagnostic signature was built using a random forest model. The area under the curve (AUC) values of this model were 0.996 and 0.886 for the training and testing sets, respectively, suggesting that the four-protein signature has a high diagnostic power. This signature was further tested with independent datasets using plasma enzyme-linked immune sorbent assays, resulting in an AUC value of 0.778 for distinguishing GC tissues from healthy controls, and using immunohistochemical tissue microarray analysis, resulting in an AUC value of 0.805. In conclusion, this study identifies potential biomarkers and improves our understanding of the pathogenesis, providing novel therapeutic targets for GC.
登录
查看更多内容
影响因子：
15.5
作者：
Nagel R;Traub RJ;Allcock RJ;Kwan MM;Bielefeldt-Ohmann H
通讯作者：
Bielefeldt-Ohmann H
影响因子：
5.2
作者：
Mukherjee S;Maitra SK
通讯作者：
Maitra SK
影响因子：
10.3
作者：
HARLOW, HJ;WEEKLEY, BL
通讯作者：
WEEKLEY, BL
DOI：
10.1099/00207713-44-4-812
发表时间：
1994-10-01
期刊：
INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY
影响因子：
--
作者：
COLLINS, MD;LAWSON, PA;FARROW, JAE
通讯作者：
FARROW, JAE
影响因子：
24.5
作者：
Jalanka-Tuovinen, Jonna;Salojarvi, Jarkko;de Vos, Willem M.
通讯作者：
de Vos, Willem M.