通过组织蛋白质组学和临床验证发现FGG作为早期胃癌的生物标志物
Identification of FGG as a Biomarker in Early Gastric Cancer via Tissue Proteomics and Clinical Verification
DOI 原文链接
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影响因子:3.6
分区:生物学2区 / 生化研究方法2区
发表日期:2024 Nov 01
作者:
Wujie Chen, Qihua Ye, Biying Zhang, Zhenhua Ma, Hanxiao Tu
DOI:
10.1021/acs.jproteome.4c00624
摘要
早期且准确诊断胃癌（GC）对降低死亡率和改善患者生活质量至关重要。然而，早期诊断GC的方法仍然缺乏。本研究采用等体标记相对和绝对定量（iTRAQ），鉴定出336个蛋白质，这些蛋白在早期胃癌（EGC）与进展性胃癌（PGC）之间表达上调的差异蛋白（DEPs）中重叠，同时在EGC与非胃癌（NGC）之间也表现出差异，且在EGC与NGC的比较中未表现出显著差异。这些DEPs主要涉及中性粒细胞相关免疫反应。蛋白质和通路的网络分析显示，纤维蛋白原α（FGA）、β（FGB）和γ（FGG）是区分EGC的候选标志物。此外，平行反应监测（PRM）、免疫组化（IHC）和Western印迹（WB）分析临床样本证实，与PGC和NGC相比，只有FGG在EGC的胃粘膜中表现出特异性且显著的上调。我们的结果表明，胃粘膜中的FGG可能成为利用内窥镜诊断EGC患者的新型生物标志物。
Abstract
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.