血清YKL-40与鳞状细胞癌抗原联合检测在食管鳞状细胞癌诊断中的应用
Establishment of using serum YKL-40 and SCCA in combination for the diagnosis of patients with esophageal squamous cell carcinoma.
作者信息
Zheng Xin, Xing Shan, Liu Xiao-Min, Liu Wen, Liu Dan, Chi Pei-Dong, Chen Hao, Dai Shu-Qin, Zhong Qian, Zeng Mu-Sheng, Liu Wan-Li
机构信息
State Key Laboratory of Oncology in Southern China, Guangzhou, China.
出版信息
BMC Cancer. 2014 Jul 7;14:490. doi: 10.1186/1471-2407-14-490.
BACKGROUND
Elevated serum YKL-40 levels have been observed in various cancers. We evaluated the diagnostic performance of serum YKL-40 alone or in combination with the CEA, CYFRA21-1 and SCCA tumor markers for patients with esophageal squamous cell carcinoma (ESCC).
METHODS
YKL-40 was detected in ESCC cell lines and tissues by real-time RT-PCR, Western blotting and ELISA. YKL-40 protein expression was determined in 20 ESCC tumor tissues using immunohistochemistry. Serum YKL-40 was measured by ELISA in 126 healthy donors, 59 patients with benign esophageal diseases and 150 patients with ESCC. Serum CEA, CYFRA21-1 and SCCA were determined by electrochemiluminescence.
RESULTS
YKL-40 mRNA and protein were observed in ESCC cancer cell lines, tissues and cell culture media, respectively. YKL-40 expression was observed in 17 of 20 ESCC samples (85%). Serum YKL-40 concentration was significantly elevated in patients with ESCC (Range: 6.95-502.10 ng/ml) compared with patients with benign diseases (Range: 1.21-429.30 ng/ml; P = 0.038) and healthy controls (Range: 2.56-132.26 ng/ml; P < 0.001). ROC curves demonstrated that serum YKL-40 has a sensitivity of 72.70%, a specificity of 84.13% and an AUC of 0.874 for the diagnosis of ESCC, which was superior to CEA (Sen: 8.00%; Spe: 96.80%, AUC = 0.652), CYFRA21-1 (Sen: 40.00%; Spe: 92.06%, AUC = 0.746) and SCCA (Sen: 32.67%; Spe: 94.44%, AUC = 0.789). The YKL-40 and SCCA combination was better for diagnosing ESCC (Sen: 82.00%, Spe: 79.37%, PPV: 82.55 and NPV: 78.74; AUC = 0.917) than the YKL-40 and CEA combination (Sen: 74.00%, Spe: 83.20%, PPV: 84.09 and NPV: 72.73; AUC = 0.877), the YKL-40 and CYFRA21-1 combination (Sen: 82.00%, Spe: 77.78%, PPV: 81.46% and NPV: 78.40%; AUC = 0.897) or the CEA, CYFRA21-1 and SCCA combination (Sen: 56.67%, Spe: 84.80%, PPV: 81.73 and NPV: 61.99; AUC = 0.831). Associations between serum YKL-40 levels and the clinic characteristics of ESCC were not significant, with the exception of age (p = 0.001).
CONCLUSIONS
ESCC tumor cells and tissues express YKL-40. Serum YKL-40 may be a potential biomarker for ESCC. Serum YKL-40 in combination with SCCA significantly increases the sensitivity of detecting ESCC.
背景
在多种癌症中均观察到血清YKL - 40水平升高。我们评估了血清YKL - 40单独或与癌胚抗原（CEA）、细胞角蛋白19片段（CYFRA21 - 1）和鳞状细胞癌抗原（SCCA）联合检测对食管鳞状细胞癌（ESCC）患者的诊断效能。
方法
采用实时逆转录聚合酶链反应（RT - PCR）、蛋白质免疫印迹法和酶联免疫吸附测定（ELISA）检测ESCC细胞系和组织中的YKL - 40。采用免疫组织化学法测定20例ESCC肿瘤组织中的YKL - 40蛋白表达。通过ELISA检测126名健康供者、59例良性食管疾病患者和150例ESCC患者的血清YKL - 40。采用电化学发光法检测血清CEA、CYFRA21 - 1和SCCA。
结果
分别在ESCC癌细胞系、组织和细胞培养基中观察到YKL - 40信使核糖核酸（mRNA）和蛋白。在20例ESCC样本中有17例（85%）观察到YKL - 40表达。与良性疾病患者（范围：1.21 - 429.30 ng/ml；P = 0.038）和健康对照者（范围：2.56 - 132.26 ng/ml；P < 0.001）相比，ESCC患者血清YKL - 40浓度显著升高。受试者工作特征（ROC）曲线表明，血清YKL - 40诊断ESCC的灵敏度为72.70%，特异度为84.13%，曲线下面积（AUC）为0.874，优于CEA（灵敏度：8.00%；特异度：96.80%，AUC = 0.652）、CYFRA21 - 1（灵敏度：40.00%；特异度：92.06%，AUC = 0.746）和SCCA（灵敏度：32.67%；特异度：94.44%，AUC = 0.789）。YKL - 40与SCCA联合检测对ESCC的诊断效能（灵敏度：82.00%，特异度：79.37%，阳性预测值：82.55，阴性预测值：78.74；AUC = 0.917）优于YKL - 40与CEA联合检测（灵敏度：74.00%，特异度：83.20%，阳性预测值：84.09，阴性预测值：72.73；AUC = 0.877）、YKL - 40与CYFRA21 - 1联合检测（灵敏度：82.00%，特异度：7
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