Long Kathryn J, Silvestri Gerard A, Kammer Michael N, Gibbs Sarah, Wu Wei, Johal Monica, Pipavath Sudhakar, Pitcher Trevor, Jett James, Nair Viswam S
Medical University of South Carolina, Charleston, SC.
Vanderbilt University Medical Center, Nashville, TN.
CHEST Pulm. 2025 Mar;3(1). doi: 10.1016/j.chpulm.2024.100130. Epub 2024 Dec 25.
Pulmonary nodules (PNs) are frequently detected by chest CT scan, which is increasingly used in clinical practice. Accurately identifying malignant nodules can pose a diagnostic challenge; therefore, a high-specificity biomarker could help clinicians identify malignant nodules and ideally lead to the earlier diagnosis of lung cancer.
What are the performance characteristics of a blood-based biomarker for identifying malignancy in patients with a CT-detected PN?
Banked plasma samples from 2 independent prospective observational cohorts of patients presenting with benign or malignant PNs 8 to 30 mm in size were tested using a 7-autoantibody panel. Sensitivity, specificity, and positive predictive value of the autoantibody test (AAT) to identify cancer were calculated for the individual and combined cohorts.
Overall, 447 patients (263 and 184 from each cohort) were included in the analysis with a prevalence of malignancy of 55%. The performance of the AAT between the 2 cohorts was similar. The AAT demonstrated a specificity of 90% (95% CI, 85%-93%), a positive predictive value of 66% (95% CI, 52%-77%), sensitivity of 16% (95% CI, 12%-22%), and false-positive rate of 10% in the combined cohort. Using a pretest probability of cancer cutoff of 20% improved the positive predictive value to 76% (95% CI, 61%-88%) and resulted in a 52% decrease in the number of false-positive test results. In the subset of patients who had 18F-fluorodeoxyglucose PET imaging performed for clinical purposes (n = 222), specificity of the AAT was higher (93% vs 58%, < .001), but the sensitivity was lower than 18F-fluorodeoxyglucose PET scan (17% vs 75%, < .001).
This study validates the specificity of a blood-based autoantibody biomarker for identifying malignancy in patients with indeterminate PNs. This rule-in biomarker may help to expedite workup of malignant nodules.
ClinicalTrials.gov; No.: NCT01752114; URL: www.clinicaltrials.gov CHEST Pulmonary 2025; 3(1):100130.
胸部CT扫描经常能检测到肺结节（PNs），其在临床实践中的应用越来越广泛。准确识别恶性结节可能带来诊断挑战；因此，一种高特异性的生物标志物有助于临床医生识别恶性结节，并理想地实现肺癌的早期诊断。
用于识别CT检测到的PN患者恶性病变的基于血液的生物标志物的性能特征是什么？
使用一个包含7种自身抗体的检测板，对来自2个独立前瞻性观察队列的、大小为8至30毫米的良性或恶性PN患者的储存血浆样本进行检测。计算了个体队列和合并队列中自身抗体检测（AAT）识别癌症的敏感性、特异性和阳性预测值。
总体而言，447例患者（每个队列各263例和184例）纳入分析，恶性病变患病率为55%。两个队列中AAT的表现相似。在合并队列中，AAT的特异性为90%（95%CI，85%-93%），阳性预测值为66%（95%CI，52%-77%），敏感性为16%（95%CI，12%-22%），假阳性率为10%。使用癌症预测试概率截断值20%可将阳性预测值提高到76%（95%CI，61%-88%），并使假阳性检测结果数量减少52%。在因临床目的进行18F-氟脱氧葡萄糖PET成像的患者亚组（n = 222）中，AAT的特异性更高（93%对58%，P <.001），但敏感性低于18F-氟脱氧葡萄糖PET扫描（17%对75%，P <.001）。
本研究验证了一种基于血液的自身抗体生物标志物在识别不确定PN患者恶性病变方面的特异性。这种纳入性生物标志物可能有助于加快恶性结节的检查。
ClinicalTrials.gov；编号：NCT01752114；网址：www.clinicaltrials.gov CHEST Pulmonary 2025；3(1):100130
