Purpose:Preclinical studies suggest that interleukin-1β (IL-1β) influences tumor behavior in non-small cell lung cancer (NSCLC). While the CANTOS trial demonstrated reduced lung cancer incidence with IL-1β inhibition, the CANOPY trials failed to show survival benefit when combined with chemoimmunotherapy. The role of IL-1β in NSCLC with oncogenic mutations remains unclear. We evaluated the prognostic and predictive significance of IL-1β expression across NSCLC subtypes.Methods:We analyzed 21,698 NSCLC tumors profiled by Caris Life Sciences using DNA and RNA next-generation sequencing. IL-1β expression was stratified into quartiles (Q1: lowest 25%, Q4: highest 25%). Real-world overall survival (OS) and time on treatment (TOT) were obtained from insurance claims. Statistical comparisons used Chi-square, Fisher’s exact, or Mann–Whitney U tests. Survival outcomes were assessed with Cox models.Results:Across unselected NSCLC patients, low IL-1β expression (Q1) was associated with modestly longer OS versus high expression (Q4) (median OS 19.5 vs. 17.4 months; HR 0.94;p< 0.0001). This effect was more pronounced in EGFR-mutant adenocarcinoma (36.7 vs. 27.2 months; HR 0.76;p< 0.001) and ALK fusion-positive NSCLC (53.0 vs. 35.2 months; HR 0.62;p= 0.002). In NSCLC without targetable mutations, IL-1β expression was not prognostic. In KRAS-mutant adenocarcinoma, high IL-1β expression was associated with modestly longer TOT on immunotherapy (7.4 vs. 6.4 months; HR 1.15;p= 0.041), but not OS. High IL-1β expression correlated positively with TP53 mutation, TMB-high, and PD-L1 expression and inversely with EGFR, KRAS, BRAF, ERBB2, KEAP1, and STK11 mutations.Conclusions:IL-1β expression is a potential prognostic and predictive biomarker in NSCLC, associated with survival outcomes in defined molecular subsets. These findings suggest that IL-1β-targeted strategies may be particularly relevant in EGFR- or ALK-altered tumors.
目的：临床前研究表明，白细胞介素-1β（IL-1β）可影响非小细胞肺癌（NSCLC）的肿瘤行为。尽管CANTOS试验证实抑制IL-1β可降低肺癌发病率，但CANOPY试验显示其与化学免疫疗法联合应用未能改善生存获益。IL-1β在携带致癌基因突变的NSCLC中的作用尚不明确。本研究评估了IL-1β表达在不同NSCLC亚型中的预后及预测价值。 方法：我们通过Caris Life Sciences公司采用DNA和RNA新一代测序技术，对21,698例NSCLC肿瘤样本进行分析。将IL-1β表达量按四分位数分层（Q1：最低25%，Q4：最高25%）。从保险理赔数据中获取真实世界总生存期（OS）和治疗持续时间（TOT）。统计学比较采用卡方检验、Fisher精确检验或Mann-Whitney U检验，生存结局通过Cox模型进行评估。 结果：在未经选择的NSCLC患者中，与高表达（Q4）相比，低IL-1β表达（Q1）与OS适度延长相关（中位OS 19.5个月 vs. 17.4个月；HR 0.94；p<0.0001）。这一效应在EGFR突变腺癌（36.7个月 vs. 27.2个月；HR 0.76；p<0.001）和ALK融合阳性NSCLC（53.0个月 vs. 35.2个月；HR 0.62；p=0.002）中更为显著。在无可靶向突变的NSCLC中，IL-1β表达无预后价值。在KRAS突变腺癌中，高IL-1β表达与免疫治疗中较长的TOT适度相关（7.4个月 vs. 6.4个月；HR 1.15；p=0.041），但与OS无关。高IL-1β表达与TP53突变、高肿瘤突变负荷（TMB-high）及PD-L1表达呈正相关，与EGFR、KRAS、BRAF、ERBB2、KEAP1和STK11突变呈负相关。 结论：IL-1β表达是NSCLC潜在的预后和预测生物标志物，与特定分子亚群的生存结局相关。这些发现提示，靶向IL-1β的治疗策略可能对EGFR或ALK基因改变的肿瘤具有特殊意义。
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