Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark; Department of Psychology and Neuroscience, Duke University, 2020 W Main St, Suite 201, Durham, NC 27708, USA.
Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Borgmester Ib Juuls Vej 1, DK-2700 Herlev, Denmark.
Clin Biochem. 2020 Oct;84:31-37. doi: 10.1016/j.clinbiochem.2020.06.001. Epub 2020 Jun 3.
Accurate first-line diagnostics are essential for early recognition of cancer but also to identify patients free of disease. The biomarker soluble urokinase plasminogen activator receptor (suPAR) is elevated in patients with cancer or non-malignant disease compared to disease-free patients. We tested if low suPAR could be used to identify disease-free patients in an accelerated cancer diagnostics program, including ruling out cancer.
Patients with serious nonspecific symptoms and signs of cancer (NSSC) were included at the Diagnostic Outpatient Clinic, Copenhagen University Hospital Hvidovre, Denmark. Data from a clinical examination, including blood tests and imaging, was combined with national registry data on diagnoses and mortality. The association between blood suPAR and the primary outcome of disease-free (i.e., absence of incident disease and mortality) within 1-year follow-up was analysed with logistic regression analysis.
Of 1583 patients included, 349 (22.0%) were diagnosed with cancer, 837 (52.9%) with non-malignant disease, and 392 (25.8%) were disease-free within one year. Admission suPAR was significantly lower in disease-free patients compared to patients with cancer or non-malignant disease (P < 0.001), area under the curve 0.67 (95% confidence interval (CI): 0.64-0.70). The highest positive predictive value (PPV) for the outcome of disease-free was 0.55 (95% CI: 0.41-0.68) at a suPAR of 1.65 ng/mL. Patients who died had significantly higher suPAR compared to patients who survived in all disease subgroups. The AUC of suPAR for 1-year mortality was 0.80 (95% CI: 0.77-0.83).
suPAR was significantly lower in disease-free individuals compared to patients with cancer or other conditions, but the PPV was not sufficiently high to terminate further clinical investigation with appropriate safety. Elevated suPAR may be a useful prognostic marker for adverse outcomes.
准确的一线诊断对于早期识别癌症以及确定无疾病患者至关重要。与无疾病患者相比，生物标志物可溶性尿激酶型纤溶酶原激活物受体 (suPAR) 在癌症或非恶性疾病患者中升高。我们测试了低 suPAR 是否可用于识别加速癌症诊断计划中的无疾病患者，包括排除癌症。
丹麦哥本哈根大学医院 Hvidovre 的诊断门诊纳入了有严重非特异性癌症症状和体征 (NSSC) 的患者。临床检查的数据，包括血液检查和影像学，与国家诊断和死亡率登记数据相结合。使用逻辑回归分析，分析血液 suPAR 与 1 年随访内无疾病（即无新发疾病和死亡率）的主要结局之间的关联。
在纳入的 1583 名患者中，349 名（22.0%）被诊断为癌症，837 名（52.9%）为非恶性疾病，392 名（25.8%）在 1 年内无疾病。与癌症或非恶性疾病患者相比，无疾病患者的入院 suPAR 显著降低（P < 0.001），曲线下面积为 0.67（95%置信区间 (CI)：0.64-0.70）。suPAR 的最高阳性预测值（PPV）为 0.55（95%CI：0.41-0.68），在 suPAR 为 1.65 ng/mL 时用于无疾病的结果。在所有疾病亚组中，死亡患者的 suPAR 显著高于存活患者。suPAR 用于 1 年死亡率的 AUC 为 0.80（95%CI：0.77-0.83）。
与癌症或其他疾病患者相比，无疾病个体的 suPAR 显著降低，但 PPV 不够高，无法终止适当安全的进一步临床调查。升高的 suPAR 可能是不良预后的有用预后标志物。
