Jeng Jen-Eing, Tsai Meng-Feng, Tsai Hey-Ru, Chuang Lea-Yea, Lin Zu-Yau, Hsieh Min-Yuh, Chen Shinn-Chern, Chuang Wan-Lung, Wang Liang-Yen, Yu Min-Lung, Dai Chia-Yen, Tsai Jung-Fa
Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
Tumour Biol. 2014 Apr;35(4):3689-98. doi: 10.1007/s13277-013-1488-2. Epub 2013 Dec 30.
This case-control study aimed to evaluate the diagnostic application of urinary transforming growth factor (TGF) α and serum α-fetoprotein (AFP) in hepatocellular carcinoma (HCC). TGFα and AFP were determined in 90 pairs of age- and gender-matched patients with cirrhotic HCC and patients with cirrhosis alone and 60 healthy controls. The results indicated that TGFα and AFP levels in patients with HCC were higher than in those with cirrhosis alone or healthy controls (each P = 0.0001). Multivariate analysis indicated that TGFα (odds ratio (OR) 1.03, 95% confidence interval (CI) 1.05-1.16) and AFP (OR 1.03, 95% CI 1.01-1.06) were closely associated, in a dose-related fashion, with the development of HCC. The optimal cutoff values, determined with the receiver operating characteristic (ROC) curves, were 29 μg/g creatinine for TGFα and 100 ng/ml for AFP, respectively. The areas under ROC curve (AUC) were 0.74 for TGFα and 0.78 for AFP, respectively. Both biomarkers showed the same sensitivity (52.2%), high specificity, high positive predictive value, and moderate positive likelihood ratio. Determination of both markers in parallel significantly increased the AUC (0.91) and diagnostic accuracy (92.2%), with a high sensitivity (86.7 %), specificity (97.8%), positive predictive value (PPV; 97.5%), and moderate positive likelihood ratio (PLR; 39.4). Among 31 cirrhotic HCC with AFP ≤ 20 ng/ml, the calculated AUC for TGFα was 0.79, with a sensitivity of 64.5%, specificity of 96.7%, PPV of 87.0%, and PLR of 19.5. In conclusion, urinary TGFα and serum AFP are complementary tumor markers for detection of HCC with low AFP production.
这项病例对照研究旨在评估尿转化生长因子（TGF）α和血清甲胎蛋白（AFP）在肝细胞癌（HCC）中的诊断应用。对90对年龄和性别匹配的肝硬化HCC患者与单纯肝硬化患者以及60名健康对照者测定了TGFα和AFP。结果表明，HCC患者的TGFα和AFP水平高于单纯肝硬化患者或健康对照者（P均=0.0001）。多变量分析表明，TGFα（比值比（OR）1.03，95%置信区间（CI）1.05 - 1.16）和AFP（OR 1.03，95%CI 1.01 - 1.06）与HCC的发生密切相关，呈剂量相关方式。通过受试者工作特征（ROC）曲线确定的最佳截断值，TGFα为29μg/g肌酐，AFP为100ng/ml。ROC曲线下面积（AUC），TGFα为0.74，AFP为0.78。两种生物标志物显示出相同的敏感性（52.2%）、高特异性、高阳性预测值和中等阳性似然比。同时测定两种标志物显著提高了AUC（0.91）和诊断准确性（92.2%），具有高敏感性（86.7%）、特异性（97.8%）、阳性预测值（PPV；97.5%）和中等阳性似然比（PLR；39.4）。在31例AFP≤20ng/ml的肝硬化HCC患者中，TGFα的计算AUC为0.79，敏感性为64.5%，特异性为96.7%，PPV为87.0%，PLR为19.5。总之，尿TGFα和血清AFP是用于检测低AFP产生的HCC的互补肿瘤标志物。
