免疫检查点抑制剂治疗患者中嗜中性粒细胞相关趋化因子染氨酸化组蛋白H3、白细胞介素-8和C-反应蛋白水平升高:对治疗反应的预测生物标志物。
Elevated levels of neutrophil related chemokine citrullinated histone H3, interleukin-8 and C-reaction protein in patients with immune checkpoint inhibitor therapy: predictive biomarkers for response to treatment.
发表日期:2023 Aug 14
作者:
Xueping Wang, Hao Huang, Lin Zhang, Yaxian Wu, Yingsheng Wen, Xuezi Weng, Qi Chen, Wanli Liu
来源:
Protein & Cell
摘要:
免疫检查点抑制剂(ICI)治疗已用于各种肿瘤。对ICI治疗反应的预测生物标志物仍不清楚,迫切需要额外和联合的生物标志物。已经评估了与肿瘤微环境(TME)相关的分泌因子,以鉴定新的非侵入性预测生物标志物。我们分析了85名进行ICI治疗的患者作为初级队列。评估了ICI反应与所有生物标记之间的关联。基于以上因素开发和验证了预测模型和标度图。77名患者被纳入验证队列。在初级队列中,非应答患者的基线血清H3Cit、IL-8和CRP水平显著高于应答患者。基于这三个因素开发了一个模型,通过以下公式计算了ICI反应的“风险评分”: “风险评分”= 3.4591×H3Cit+2.5808×IL8+2.0045×CRP-11.3844。 “风险评分”的截断点为0.528, “风险评分”低于0.528的患者更有可能受益于ICI治疗(AUC:0.937,95% CI:0.886-0.988,敏感性80.60%,特异性91.40%)。在验证队列中,该AUC为0.719(95% CI:0.600-0.837,P=0.001),敏感性为70.00%,特异性为65.20%。结合了H3Cit、IL-8和CRP的模型对ICI反应具有出色的预测能力,因此风险评分较低的患者选择性地受益于ICI治疗,这对于早期检测ICI反应具有重要的临床意义。©2023年。BioMed Central有限公司,斯普林格自然出版集团的一部分。
Immune checkpoint inhibitor (ICI) therapy has been used in various tumors. The biomarkers predictive of a response to ICI treatment remain unclear, and additional and combined biomarkers are urgently needed. Secreted factors related to the tumor microenvironment (TME) have been evaluated to identify novel noninvasive predictive biomarkers.We analyzed 85 patients undergoing ICI therapy as the primary cohort. The associations between ICI response and all biomarkers were evaluated. A prediction model and a nomogram were developed and validated based on the above factors.Seventy-seven patients were enrolled in the validation cohort. In the primary cohort, the baseline serum levels of H3Cit, IL-8 and CRP were significantly higher in nonresponder patients. A model based on these three factors was developed, and the "risk score" of an ICI response was calculated with the formula: "risk score" = 3.4591×H3Cit + 2.5808×IL8 + 2.0045 ×CRP- 11.3844. The cutoff point of the "risk score" was 0.528, and patients with a "risk score" lower than 0.528 were more likely to benefit from ICI treatment (AUC: 0.937, 95% CI: 0.886-0.988, with sensitivity 80.60%, specificity 91.40%). The AUC was 0.719 (95% CI: 0.600-0.837, P = 0.001), with a sensitivity of 70.00% and specificity of 65.20% in the validation cohort.A model incorporating H3Cit, IL-8 and CRP has an excellent prediction ability for ICI response; thus, patients with a lower "risk score" selectively benefit from ICI treatment, which may have significant clinical implications for the early detection of an ICI response.© 2023. BioMed Central Ltd., part of Springer Nature.