Kim Dong Su, Ham Won Sik, Jang Won Sik, Cho Kang Su, Choi Young Deuk, Kang Suki, Kim Bora, Kim Kook Jin, Lim Eun Ji, Rha Sun Young, Ku Ja Hyeon, Kwak Cheol, Kim Hyeon Hoe, Jeong Chang Wook, Cho Nam Hoon
Genomine Research Division, Genomine, Inc., Pohang Technopark, Pohang, Kyungbuk 790-834, Korea.
Department of Urology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.
Diagnostics (Basel). 2020 Sep 25;10(10):750. doi: 10.3390/diagnostics10100750.
The early detection of renal cell carcinoma (RCC) using tumor markers remains an attractive prospect for the potential to downstage the disease. To validate the scale-up clinical performance of potential tumor markers for RCC (as a single marker and as a composite tumor marker composed of nicotinamide N-methyltransferase (NNMT), L-Plastin (LCP1), and non-metastatic cells 1 protein (NM23A)), the scale-up assay was performed. Patients with RCC from multiple domestic institutes were included in the clinical evaluation for reassessment and improvement of the established triple markers of our product. For the diagnostic performance of the composite markers, the best-split cutoff points of each marker (147 pg/mL for NNMT, 1780 pg/mL for LCP1, and 520 pg/mL for NM23A) were installed. Serum levels of NNMT, LCP1, and NM23A were greatly increased in subjects with RCC ( < 0.0001). In 1042 blind sample tests with control individuals (n = 500) and patients with RCC (n = 542), the diagnostic sensitivity and specificity of the composite three-marker assay were 0.871 and 0.894, respectively, and the resulting AUC (Area under Curve) of ROC (Receiver Operating Characteristic) was 0.917. As a single marker, the diagnostic accuracies of NNMT, LCP1, and NM23A, as estimated by ROC, were 0.833, 0.844, and 0.601, respectively. The composite three-marker assay with NNMT, LCP1, and NM23A is a more improved novel serum marker assay for the early detection of RCC in cases of renal mass or unknown condition. The NNMT, LCP1, and NM23A triple marker assay could be a powerful diagnostic tumor marker assay to screen the early stage of RCC.
利用肿瘤标志物早期检测肾细胞癌（RCC），因其有可能降低疾病分期，仍是一个颇具吸引力的前景。为验证肾细胞癌潜在肿瘤标志物（作为单一标志物以及由烟酰胺N-甲基转移酶（NNMT）、L-原肌球蛋白（LCP1）和非转移性细胞1蛋白（NM23A）组成的复合肿瘤标志物）放大规模后的临床性能，进行了放大检测。来自多个国内机构的肾细胞癌患者被纳入临床评估，以重新评估和改进我们产品已确立的三联标志物。对于复合标志物的诊断性能，设定了每个标志物的最佳分割临界值（NNMT为147 pg/mL，LCP1为1780 pg/mL，NM23A为520 pg/mL）。肾细胞癌患者的NNMT、LCP1和NM23A血清水平大幅升高（<0.0001）。在对500名对照个体和542名肾细胞癌患者进行的1042次盲样检测中，复合三联标志物检测的诊断敏感性和特异性分别为0.871和0.894，所得的ROC（受试者工作特征）曲线下面积（AUC）为0.917。作为单一标志物，经ROC估计，NNMT、LCP1和NM23A的诊断准确率分别为0.833、0.844和0.601。由NNMT、LCP1和NM23A组成的复合三联标志物检测是一种经过改进的新型血清标志物检测方法，用于在肾肿块或病情不明的情况下早期检测肾细胞癌。NNMT、LCP1和NM23A三联标志物检测可能是一种强大的诊断肿瘤标志物检测方法，用于筛查肾细胞癌的早期阶段。
