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心肌肌球蛋白结合蛋白C在免疫治疗相关心血管不良事件中的诊断价值

Diagnositic performance of cardiac myosin-binding protein C in cardiovascular immune-related adverse events

    摘要
  • 摘要:
    目的 探讨心肌肌球蛋白结合蛋白C（cardiac myosin-binding protein C, cMyBP-C）在免疫治疗相关心血管不良事件（cardiovascular immune-related adverse event, CV-irAE）中的诊断性能，评估其作为新型泛心肌损伤生物标志物在临床中的应用价值。
    方法 纳入2025年1月至2025年9月于复旦大学附属中山医院接受免疫检查点抑制剂（immune checkpoint inhibitor, ICI）治疗的肿瘤患者，根据高敏肌钙蛋白T（high-sensitivity cardiac troponin T, hs-cTnT）水平分为阳性组≥第99百分位数（14 pg/mL），n＝78与阴性组（＜第99百分位数，n＝56）。另纳入未接受抗肿瘤治疗的肿瘤确诊患者及健康体检者共231例作为对照组。检测各组cMyBP-C、hs-cTnT、肌酸激酶同工酶MB（creatine kinase isoenzyme-MB，CK-MB）、氨基末端脑钠肽前体（N-terminal pro-brain natriuretic peptide, NT-proBNP）等指标水平。采用百分位数法建立cMyBP-C筛查参考值。通过受试者工作特征（receiver operating characteristic, ROC）曲线及曲线下面积（area under the curve, AUC）评估cMyBP-C诊断性能。采用Spearman法分析cMyBP-C与心脏磁共振（cardiac magnetic resonance, CMR）所示心肌水肿程度的关系。
    结果 3组cMyBP-C水平差异有统计学意义（P＜0.001）。基于对照组第99百分位数确定的cMyBP-C诊断参考值为5.86 pg/mL。ROC分析显示，cMyBP-C诊断CV-irAE的AUC为0.919（95%CI 0.898～0.939），与CK-MB（AUC＝0.917，95%CI 0.896～0.939，P＝0.682）相当，优于NT-proBNP（AUC＝0.876，95%CI 0.850～0.902，P＜0.001）。排除非CV-irAE患者后，cMyBP-C的AUC提高至0.934，CK-MB为0.893、NT-proBNP为 0.877。Spearman相关性分析显示，在ICI相关心肌炎患者中，cMyBP-C水平与CMR评估的心肌水肿程度正相关（ρ＝0.64，P＝0.002）。
    结论 cMyBP-C在ICI治疗后CV-irAE患者中升高，具有与传统标志物可比或更优的诊断性能，且能反映心肌炎症负荷，提示其可作为CV-irAE诊断的有效补充标志物。

     

    Abstract:
    Objective To investigate the diagnositic performance of cardiac myosin-binding protein C (cMyBP-C) in cardiovascular immune-related adverse events (CV-irAE), and to evaluate its potential as a novel biomarker of myocardial injury.
    Methods Cancer patients receiving immune checkpoint inhibitors (ICI) therapy at Zhongshan Hospital, Fudan University, from January 2025 to September 2025 were enrolled. Patients were divided into the positive group (high-sensitivity cardiac troponin T hs-cTnT≥99th percentile 14 pg/mL, n＝78) and the negative group (hs-cTnT＜99th percentile, n＝56). A control group (n＝231) consisted of cancer patients without prior anti-tumor therapy and healthy individuals. Levels of cMyBP-C, hs-cTnT, creatine kinase isoenzyme-MB (CK-MB), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured. The screening reference value of cMyBP-C was established using the 99th percentile method. Diagnositic performance was evaluated by receiver operating characteristic (ROC) curves and area under the curve (AUC). The association between cMyBP-C level and myocardial edema assessed by cardiac magnetic resonance (CMR) was analyzed using Spearman correlation.
    Results The difference in cMyBP-C levels among the three groups was statistically significant (P＜0.001). Based on the 99th percentile of the control group, the screening reference value of cMyBP-C was determined to be 5.86 pg/mL. ROC curves showed that cMyBP-C achieved an AUC of 0.919 (95%CI 0.898–0.939) for detecting the risk of CV-irAE, comparable to CK-MB (AUC＝0.917, 95%CI 0.896–0.939, P＝0.682) and superior to NT-proBNP (AUC＝0.876, 95%CI 0.850–0.902, P＜0.001). After excluding non-cardiovascular adverse events, the AUC of cMyBP-C increased to 0.934, CK-MB was 0.893, and NT-proBNP was 0.877. Spearman correlation analysis revealed that among patients with ICI-associated myocarditis (n＝21), cMyBP-C level was positively correlated with the extent of myocardial edema assessed by CMR ( ρ＝0.64, P＝0.002).
    Conclusions cMyBP-C is significantly elevated in patients with CV-irAEs, demonstrating diagnositic performance comparable to or better than conventional biomarkers, and reflecting the burden of myocardial inflammation. These findings suggest that cMyBP-C may serve as a valuable complementary diagnositic biomarker for CV-irAEs.

     

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