Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands.
Front Immunol. 2023 Mar 15;14:1125658. doi: 10.3389/fimmu.2023.1125658. eCollection 2023.
Previous evidence indicated that -induced inflammation is the first step towards gastric carcinogenesis. However, investigations of the immunological factors driving this process have shown inconsistencies. We aimed to present a thorough summary of all researched cytokines in relation to infection and GC and relate these to global GC risk.
We performed a systematic review and tandem meta-analysis identifying all published studies reporting on serum cytokine levels in -infected cases vs. non-infected controls and gastric cancer cases vs. non-gastric cancer controls, with sub-analyses performed to identify global regional differences in cytokine induction and their correlation with GC incidence.
Only levels of systemic IL-6 (standardized mean difference [SMD]:0.95, 95%CI [0.45;1.45]) and TNF-α (SMD:0.88, 95%CI [0.46; 1.29]) were significantly increased upon infection. Sub-analysis showed that of IL-6 levels were increased upon infection in East Asian, Middle Eastern and Southeast Asian cohorts, but not in North America, Europe, Russia and Africa. Serum levels of IL-6, IL-7, IL-10, IL-12, and TNF-α were significantly raised in GC. Exploration of the relationship between serum cytokines changes upon infection and regional differences in risk of GC development indicated that the SMD of IL-6 serum levels presents a significant correlation with the relative incidence of GC (=0.81, =0.00014).
This study shows that infection and GC are associated with increased IL-6 and TNF-α levels. Particularly, IL-6 shows region-specific increases that correlate with GC incidence, making it a key contender for the cause of this disease.
先前的证据表明，幽门螺杆菌引起的炎症是胃癌发生的第一步。然而，对驱动这一过程的免疫因素的研究显示出不一致性。我们旨在全面总结与幽门螺杆菌感染和 GC 相关的所有研究细胞因子，并将这些与全球 GC 风险联系起来。
我们进行了系统评价和串联荟萃分析，确定了所有发表的研究报告，这些研究报告报道了感染病例与非感染对照、胃癌病例与非胃癌对照之间的血清细胞因子水平，并进行了亚分析，以确定细胞因子诱导的全球区域差异及其与 GC 发生率的相关性。
只有系统性白细胞介素 6（标准化均数差 [SMD]：0.95，95%置信区间 [0.45；1.45]）和肿瘤坏死因子-α（SMD：0.88，95%置信区间 [0.46；1.29]）的水平在幽门螺杆菌感染后显著升高。亚分析显示，东亚、中东和东南亚队列的白细胞介素 6 水平在幽门螺杆菌感染后升高，但在北美、欧洲、俄罗斯和非洲则没有。胃癌患者的血清白细胞介素 6、白细胞介素 7、白细胞介素 10、白细胞介素 12 和肿瘤坏死因子-α水平显著升高。探索幽门螺杆菌感染后血清细胞因子变化与 GC 发病风险的区域差异之间的关系表明，白细胞介素 6 血清水平的 SMD 与 GC 的相对发病率呈显著相关（=0.81，=0.00014）。
本研究表明，幽门螺杆菌感染和 GC 与白细胞介素 6 和肿瘤坏死因子-α水平升高有关。特别是，白细胞介素 6 表现出与 GC 发病率相关的区域特异性升高，使其成为该疾病病因的重要候选者。
