PO.CL01.17 · 临床研究
IL-6和IL-8在IV期胃癌患者中的预后及转移相关作用
Prognostic and metastasis-associated roles of IL-6 and IL-8 in patients with stage IV gastric cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：细胞因子驱动的炎症日益被认为是胃癌肿瘤进展和转移行为的关键决定因素。白细胞介素-6（IL-6）和白细胞介素-8（IL-8）是免疫抑制、血管生成和全身炎症激活的核心介质，然而其在晚期胃癌中的临床意义仍未充分明确。
方法：分析了2019年5月至2025年3月在Severance医院接受治疗的186例HER2阴性IV期胃癌患者的治疗前血液样本。在IV期胃癌患者接受全身治疗前，通过ELISA定量检测血清IL-6和IL-8水平。使用预先设定的临界值将患者分为高表达组和低表达组。使用PD-L1 IHC 22C3 pharmDx检测通过免疫组织化学评估PD-L1表达，并以联合阳性评分（CPS）进行定量。使用非参数检验和Kaplan-Meier分析评估其与转移模式及总生存期（OS）的关联。
结果：高细胞因子表达与较差的临床结局密切相关。IL-6水平高（≥4.6862 pg/mL）的患者OS较IL-6低组显著缩短（HR 1.96，95% CI 1.31-2.94；P=0.0008）。IL-8也观察到类似但更显著的效应，其高表达（≥7.5801 pg/mL）与显著更差的生存相关（HR 2.79，95% CI 1.89-4.10；P < 0.0001）。在任何CPS临界值下，均未观察到IL-6与PD-L1表达之间或IL-8与PD-L1表达之间的相关性。细胞因子水平还表现出转移模式的特异性：IL-6在骨转移患者中显著升高（P = 0.018），IL-8亦然（P = 0.039），而IL-8在肝转移患者中显著增高（P = 0.002）。这些发现提示，全身细胞因子升高既反映了肿瘤的侵袭性，也反映了不同的转移表型。
结论：IL-6和IL-8是与晚期胃癌不良生存和特征性转移模式相关的有力且易于获取的生物标志物。将其纳入临床风险评估可能改善生物学分层，并为未来的治疗策略提供依据。
查看英文原文 English abstract
Background: Cytokine-driven inflammation is increasingly recognized as a key determinant of tumor progression and metastatic behavior in gastric cancer. Interleukin-6 (IL-6) and interleukin-8 (IL-8) are central mediators of immune suppression, angiogenesis, and systemic inflammatory activation, yet their clinical significance in advanced gastric cancer remains insufficiently defined.
Methods: Pre-treatment blood samples from 186 patients with HER2-negative stage IV gastric cancer treated at Severance Hospital between May 2019 and March 2025 were analyzed. Serum IL-6 and IL-8 levels were quantified by ELISA in patients with stage IV gastric cancer prior to systemic therapy. Patients were stratified into high- and low-expression groups using predefined cutoffs. PD-L1 expression was assessed by immunohistochemistry using the PD-L1 IHC 22C3 pharmDx assay and quantified by combined positive score (CPS). Associations with metastatic patterns and overall survival (OS) were assessed using nonparametric tests and Kaplan-Meier analysis.
Results: High cytokine expression was strongly associated with inferior clinical outcomes. Patients with high IL-6 levels (≥4.6862 pg/mL) showed significantly reduced OS compared with the IL-6-low group (HR 1.96, 95% CI 1.31-2.94; P=0.0008). A similar but more pronounced effect was observed for IL-8, where high expression (≥7.5801 pg/mL) was associated with markedly worse survival (HR 2.79, 95% CI 1.89-4.10; P < 0.0001). No correlation was observed between IL-6 and PD-L1 expression or between IL-8 and PD-L1 expression at any CPS cutoff. Cytokine levels also demonstrated metastatic pattern specificity: IL-6 was significantly elevated in patients with bone metastasis (P = 0.018) including IL-8 (P = 0.039), whereas IL-8 was markedly increased in those with liver metastasis (P = 0.002). These findings suggest that systemic cytokine elevation reflects both tumor aggressiveness and distinct metastatic phenotypes.
Conclusion: IL-6 and IL-8 are strong, accessible biomarkers associated with poor survival and characteristic metastatic patterns in advanced gastric cancer. Their integration into clinical risk assessment may improve biological stratification and inform future therapeutic strategies.
利益披露 Disclosure
J. Jang, None..
C. Park, None..
W. Kwon, None..
T. Kim, None.