BACKGROUND Localized C3 deposition is a well-known factor of inflammation. However, its role in oncoprogression of gastric cancer (GC) remains obscured. This study aims to explore the prognostic value of C3 deposition and to elucidate the mechanism of C3-related oncoprogression for GC. METHODS From August to December 2013, 106 GC patients were prospectively included. The regional expression of C3 and other effectors in gastric tissues were detected by WB, IHC, qRT-PCR and other tests. The correlation of localized C3 deposition and oncologic outcomes was determined by 5-year survival significance. Human GC and normal epithelial cell lines were employed to detect a relationship between C3 and STAT3 signaling pathway in vitro experiments. RESULTS C3 and C3a expression were markedly enhanced in GC tissues at both mRNA and protein levels compared with those in paired nontumorous tissues. According to IHC C3 score, 65 (61.3%) and 41 (38.7%) patients had high and low C3 deposition, respectively. C3 deposition was negatively correlated with plasma levels of C3 and C3a (both P < 0.001) and positively correlated with pathological T and TNM stages (both P < 0.001). High C3 deposition was identified as an independent prognostic factor of poor 5-year overall survival (P = 0.045). In vitro C3 administration remarkably enhanced p-JAK2/p-STAT3 expression in GC cell lines but caused a reduction of such activation when pre-incubated with a C3 blocker. Importantly, C3 failed to activate such signaling in cells pre-treated with a JAK2 inhibitor. CONCLUSIONS Localized C3 deposition in the tumor microenvironment is a relevant immune signature for predicting prognosis of GC. It may aberrantly activate JAK2/STAT3 pathway allowing oncoprogression. TRIAL REGISTRATION ClinicalTrials.gov, NCT02425930, Registered 1st August 2013.

中文翻译：

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补体C3过表达激活JAK2 / STAT3途径并与胃癌进展相关。

背景技术局部C3沉积是炎症的众所周知的因素。但是，其在胃癌（GC）进展中的作用仍然被掩盖。本研究旨在探讨C3沉积的预后价值，并阐明C3相关的肿瘤进展机制。方法从2013年8月至2013年12月，前瞻性纳入106例GC患者。通过WB，IHC，qRT-PCR和其他测试检测了C3和其他效应子在胃组织中的区域表达。局部C3沉积与肿瘤学结局的相关性由5年生存率确定。在体外实验中，使用人GC和正常上皮细胞系检测C3和STAT3信号通路之间的关系。结果与配对的非肿瘤组织相比，GC组织中的mRNA和蛋白质水平均显着增强了C3和C3a的表达。根据IHC C3评分，分别有65例（61.3％）和41例（38.7％）的C3沉积高和低。C3沉积与血浆C3和C3a水平呈负相关（均P <0.001），与病理T和TNM分期呈正相关（均P <0.001）。较高的C3沉积被确定为5年总生存期较差的独立预后因素（P = 0.045）。体外C3给药显着增强了GC细胞系中p-JAK2 / p-STAT3的表达，但与C3阻断剂预温育后导致此类激活的减少。重要的是，C3无法在用JAK2抑制剂预处理的细胞中激活此类信号传导。结论肿瘤微环境中的局部C3沉积是预测GC预后的相关免疫信号。它可能异常激活JAK2 / STAT3途径，从而使肿瘤进展。试验注册ClinicalTrials.gov，NCT02425930，2013年8月1日注册。