Background/Objectives: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy; however, reliable biomarkers of therapeutic efficacy remain limited. We investigated the clinical utility of plasma WFDC2 levels in patients receiving anti-PD-1 antibody treatment.Methods: Twenty-one patients with non-small cell lung, gastric, or bladder cancer received nivolumab or pembrolizumab. Plasma WFDC2 concentrations were measured by ELISA before ICI treatment (pre-ICI) and after two and four treatment cycles. Associations between WFDC2 expression changes and overall survival (OS), progression-free survival (PFS), and tumor progression were assessed. ROC curve analyses compared the predictive performance of WFDC2, soluble PD-L1 (sPD-L1), soluble PD-1 (sPD-1), and their combinations, with the area under the curve (AUC) evaluating predictive accuracy.Results: Levels of WFDC2 pre-ICI and those after two cycles were significantly higher than levels in healthy donors. However, no significant differences in WFDC2 levels were found between the time points during treatment. Greater increases in WFDC2 levels were significantly correlated with shorter OS (p= 0.002), shorter PFS (p= 0.037), and tumor progression (p= 0.003). ROC analysis revealed that WFDC2 achieved a higher AUC (0.700) than sPD-L1 (0.538) or sPD-1 (0.650). Combining biomarkers improved the predictive accuracy, with sPD-L1 plus WFDC2 showing the highest AUC (0.825).Conclusions: Serial increases in plasma WFDC2 are associated with poor clinical outcomes, highlighting its potential as a biomarker. Baseline plasma WFDC2 outperformed sPD-L1 and sPD-1 diagnostically. These findings should be interpreted as exploratory and hypothesis-generating, requiring confirmation in larger, tumor-specific cohorts with multivariate adjustment. WFDC2 represents a promising minimally invasive biomarker for the early identification of patients unlikely to benefit from ICI therapy.
**背景/目的：** 免疫检查点抑制剂（ICIs）已彻底改变了癌症治疗，但可靠的治疗疗效生物标志物仍然有限。本研究探讨了血浆WFDC2水平在接受抗PD-1抗体治疗患者中的临床应用价值。 **方法：** 21名患有非小细胞肺癌、胃癌或膀胱癌的患者接受了纳武利尤单抗或帕博利珠单抗治疗。在ICI治疗前（ICI前）以及治疗两个周期和四个周期后，通过ELISA法测量血浆WFDC2浓度。评估了WFDC2表达变化与总生存期（OS）、无进展生存期（PFS）和肿瘤进展之间的关联。通过ROC曲线分析比较了WFDC2、可溶性PD-L1（sPD-L1）、可溶性PD-1（sPD-1）及其组合的预测性能，并使用曲线下面积（AUC）评估预测准确性。 **结果：** ICI前和治疗两个周期后的WFDC2水平均显著高于健康供者。然而，治疗期间各时间点的WFDC2水平未发现显著差异。WFDC2水平增幅越大，与更短的OS（p=0.002）、更短的PFS（p=0.037）以及肿瘤进展（p=0.003）显著相关。ROC分析显示，WFDC2的AUC（0.700）高于sPD-L1（0.538）或sPD-1（0.650）。组合生物标志物提高了预测准确性，其中sPD-L1联合WFDC2显示出最高的AUC（0.825）。 **结论：** 血浆WFDC2的连续升高与不良临床结局相关，突显了其作为生物标志物的潜力。基线血浆WFDC2在诊断性能上优于sPD-L1和sPD-1。这些发现应被视为探索性和假设生成性的，需要在更大的、肿瘤特异性队列中进行多变量调整后的验证。WFDC2代表了一种有前景的微创生物标志物，可用于早期识别可能无法从ICI治疗中获益的患者。
肿瘤(癌症)患者之家