通过组织蛋白质组学和临床验证确定 FGG 作为早期胃癌的生物标记物

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-10-17 DOI:10.1021/acs.jproteome.4c0062410.1021/acs.jproteome.4c00624
Wujie Chen, Qihua Ye, Biying Zhang, Zhenhua Ma* and Hanxiao Tu*, 
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引用次数: 0

摘要

胃癌(GC)的早期准确诊断对于降低死亡率和改善患者福祉至关重要。然而,目前仍缺乏早期诊断胃癌的方法。在这项研究中,通过等位标记相对和绝对定量(iTRAQ)技术,我们在早期胃癌(EGC)与进展期胃癌(PGC)的上调差异表达蛋白(DEPs)、EGC与非胃癌(NGC)的上调差异表达蛋白(DEPs)以及EGC与NGC的非显著蛋白中发现了336个重叠蛋白。这些DEPs主要参与中性粒细胞相关的免疫反应。蛋白质和通路网络分析显示,纤维蛋白原α(FGA)、β(FGB)和γ(FGG)是区分EGC的候选蛋白。此外,对临床样本进行的平行反应监测(PRM)、免疫组织化学(IHC)和免疫印迹(WB)检测证实,与PGC和NGC相比,只有FGG在EGC胃粘膜中独特地显著上调。我们的研究结果表明,胃黏膜中的FGG可作为一种新型生物标记物,通过内镜诊断EGC患者。
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Identification of FGG as a Biomarker in Early Gastric Cancer via Tissue Proteomics and Clinical Verification

Early and accurate diagnosis of gastric cancer (GC) is essential for reducing mortality and improving patient well-being. However, methods for the early diagnosis of GC are still lacking. In this study, by isobaric tagging for relative and absolute quantitation (iTRAQ), we identified 336 proteins that overlapped among the upregulated differentially expressed proteins (DEPs) in early gastric cancer (EGC) versus progressive gastric cancer (PGC), upregulated DEPs in EGC versus nongastric cancer (NGC), and nonsignificant proteins in EGC versus NGC. These DEPs were involved primarily in the neutrophil-related immune response. Network analysis of proteins and pathways revealed that fibrinogen α (FGA), β (FGB), and γ (FGG) are candidates for distinguishing EGC. Furthermore, parallel reaction monitoring (PRM), immunohistochemistry (IHC), and Western blot (WB) assays of clinical samples confirmed that, compared with that in PGC and NGC, only FGG was uniquely and significantly upregulated in the gastric mucosa of EGC. Our results demonstrated that FGG in the gastric mucosa could be a novel biomarker to diagnose EGC patients via endoscopy.

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