Background/Objectives:Tumor-immune system interactions shape the progression of cutaneous squamous cell carcinoma (cSCC). Serum biomarkers for risk stratification remain limited. Complement factor H (CFH) regulates the alternative complement pathway. It has been linked to immunosuppression and cSCC development in tissue-based studies. We investigated whether serum CFH is associated with tumor aggressiveness and may help predict immunotherapy outcomes in advanced cSCC.Methods:In this retrospective, single-center study, pre-treatment serum CFH levels were measured in 104 cSCC patients (62 high-risk and 42 advanced) using ELISA. Associations with clinical characteristics, disease stage, and response to cemiplimab were analyzed. Subgroup comparisons considered immune status and inflammatory comorbidities.Results:Advanced cSCC patients had significantly higher CFH levels than high-risk patients (OR 0.13,p= 0.026), independent of tumor diameter or invasion depth. Among advanced cSCC cases, lower baseline CFH was associated with more prolonged progression-free survival (median 19.8 vs. 3.07 months,p= 0.029; HR 0.29,p= 0.014), independent of covariates including immunosuppression. CFH levels during therapy did not predict treatment response. ROC analysis showed moderate discriminatory ability with CFH alone (AUC 0.625), which improved when combined with clinical variables in a multivariable risk model (AUC 0.767).Conclusions:Serum CFH is an independent predictor of cemiplimab response and reflects biological aggressiveness in cSCC beyond conventional high-risk features. These findings support the use of CFH in clinical risk models and warrant external validation in multicenter cohorts.
背景/目的：肿瘤与免疫系统的相互作用影响皮肤鳞状细胞癌（cSCC）的进展。目前用于风险分层的血清生物标志物仍较为有限。补体因子H（CFH）可调控补体旁路途径。基于组织学的研究已发现其与免疫抑制及cSCC发展相关。本研究旨在探讨血清CFH是否与肿瘤侵袭性相关，并可能有助于预测晚期cSCC的免疫治疗疗效。 方法：在这项回顾性单中心研究中，采用ELISA法检测了104例cSCC患者（62例高风险患者和42例晚期患者）治疗前的血清CFH水平。分析了CFH水平与临床特征、疾病分期及对cemiplimab治疗反应之间的关联。亚组比较考虑了免疫状态和炎症性合并症的影响。 结果：晚期cSCC患者的CFH水平显著高于高风险患者（OR 0.13，p=0.026），且该关联独立于肿瘤直径或浸润深度。在晚期cSCC病例中，较低的基线CFH水平与更长的无进展生存期相关（中位生存期19.8个月 vs. 3.07个月，p=0.029；HR 0.29，p=0.014），且该关联独立于包括免疫抑制在内的协变量。治疗期间的CFH水平未能预测治疗反应。ROC分析显示，单独使用CFH具有中等区分能力（AUC 0.625），而在多变量风险模型中结合临床变量后，区分能力有所提升（AUC 0.767）。 结论：血清CFH是cemiplimab治疗反应的独立预测因子，并反映了cSCC超越传统高风险特征的生物学侵袭性。这些发现支持将CFH纳入临床风险模型，并有必要在多中心队列中进行外部验证。
肿瘤(癌症)患者之家