Table4_Serum proteomic profiling of precancerous gastric lesions and early gastric cancer reveals signatures associated with systemic inflammatory response and metaplastic differentiation.XLSX

The noninvasive detection technique using serum for large-scale screening is useful for the early diagnosis of gastric cancer (GC). Herein, we employed liquid chromatography mass spectrometry to determine the serum proteome signatures and related pathways in individuals with gastric precancerous (pre-GC) lesions and GC and explore the effect of Helicobacter pylori (H. pylori) infection. Differentially expressed proteins in GC and pre-GC compared with non-atrophic gastritis (NAG) group were identified. APOA4, a protein associated with metaplastic differentiation, and COMP, an extracellular matrix protein, were increased in the serum of patients with pre-GC lesions and GC. In addition, several inflammation-associated proteins, such as component C3, were decreased in the GC and pre-GC groups, which highlight a tendency for the inflammatory response to converge at the gastric lesion site during the GC cascade. Moreover, the abundance of proteins associated with oxidant detoxification was higher in the GC group compared with that in the NAG group, and these proteins were also increased in the serum of the H. pylori-positive GC group compared with that in the H. pylori-negative GC patients, reflecting the importance of oxidative stress pathways in H. pylori infection. Collectively, the findings of this study highlight pathways that play important roles in GC progression, and may provide potential diagnostic biomarkers for the detection of pre-GC lesions.

利用血清开展大规模筛查的无创检测技术，可用于胃癌（gastric cancer，GC）的早期诊断。本研究采用液相色谱-质谱联用法（liquid chromatography mass spectrometry），对胃癌前病变（gastric precancerous lesions，pre-GC）患者与胃癌患者的血清蛋白质组特征及相关通路进行分析，并探讨幽门螺杆菌（Helicobacter pylori，H. pylori）感染的影响。研究鉴定出相较于非萎缩性胃炎（non-atrophic gastritis，NAG）组，胃癌及胃癌前病变组中差异表达的蛋白质。其中，与化生分化相关的蛋白质APOA4，以及细胞外基质蛋白COMP，在胃癌前病变与胃癌患者的血清中表达上调。此外，胃癌及胃癌前病变组中多种炎症相关蛋白（如补体C3（component C3））的表达水平下调，这提示在胃癌发生的级联过程中，炎症应答存在向胃部病变部位聚集的趋势。进一步分析发现，相较于非萎缩性胃炎组，胃癌组中与抗氧化解毒相关的蛋白质丰度更高；且幽门螺杆菌阳性胃癌患者的血清中，此类蛋白质的丰度也高于幽门螺杆菌阴性胃癌患者，这反映出氧化应激通路在幽门螺杆菌感染过程中的重要作用。综上，本研究的结果明确了在胃癌进展过程中发挥关键作用的通路，可为胃癌前病变的检测提供潜在的诊断生物标志物。