基于自然人群队列解析血清微量元素及炎症蛋白组诱导胃癌的风险与功能验证

近期研究报道多种微量元素暴露水平可能与胃癌发生相关，为胃癌病因学研究提供了新思路。申请者前期研究也发现，与健康对照相比，胃癌患者头发和指甲中多种微量元素水平存在显著差异。由于既往研究多为横断面关联性研究，故在进行因果推断时受限，且关联背后潜在的生物学机制尚不清楚。炎症是肿瘤发生的关键生物学机制之一，研究提示暴露于不同水平的微量元素可通过促进或抑制炎症反应来参与肿瘤发生发展过程，但仍处于初步研究阶段。基于此，申请者提出微量元素暴露通过引发炎症蛋白谱变化来参与胃癌发生发展的研究假设，并拟通过人群队列与动物实验相结合，深入验证并探索研究假设：阐明微量元素暴露及其相关炎症蛋白变化在胃癌发生中的作用，绘制微量元素暴露-炎症蛋白变化关联图谱，并进一步通过小鼠模型验证与探索潜在分子机制。研究结果将为解析胃癌病因以及胃癌防治策略的制定提供科学依据。

Recent studies have reported that the exposure levels of multiple trace elements might be associated with the development of gastric cancer (GC), which provides a new idea for the study of the etiology of GC. Our previous study also found that compared with healthy controls, significant differences were observed in GC cases in the levels of trace elements of hairs and fingernails. However, previous studies are mostly cross-sectional correlation studies, which is difficult to infer the causal relationship; and the underlying biological mechanism behind the correlation is unclear. Inflammation is one of the key biological mechanisms of tumorigenesis. Studies suggest that exposure to different levels of trace elements can participate in tumorigenesis by promoting or inhibiting inflammatory responses, however, this is still in the preliminary research stage. Based on this, we hypothesize that trace elements exposure participates in the development of GC by triggering changes in the inflammation-related protein profiles. We intend to further verify and explore the research hypothesis through population cohort study and animal experiments: to clarify the role of trace elements exposure and inflammation-related protein changes in the development of GC, draw an association profile of trace elements exposure with inflammation protein changes, and further verify and explore the underlying mechanism using mice model. The study results can provide a scientific basis for enriching the etiology of GC and formulating prevention and treatment strategies for GC.