Xu Cheng, Zeng Xiang-Hua, Wang Li, Tao Shi-Qi, Wu Quan-Xin, Zhu Peng, Deng Guo-Hong, Wang Yu-Ming
Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University; Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing 400038, China.
Hepatobiliary Pancreat Dis Int. 2015 Apr;14(2):164-70. doi: 10.1016/s1499-3872(15)60352-6.
The current methods used for diagnosing hepatocellular carcinoma (HCC) are unsatisfactory. Here, we assessed the serum levels of secreted frizzled related protein 4 (sFRP-4) for diagnosing HCC in patients infected with chronic hepatitis B (CHB).
In 272 patients with CHB enrolled, 142 were patients with HCC. Thirty-three healthy subjects were recruited as healthy controls. The CHB patients were assigned to a test group or a validation group based on the time of enrollment. Human antibody arrays were used to screen 15 patients (8 CHB-related HCC patients, 7 CHB patients) for serum markers. Four markers and one candidate marker were assessed in the test group and validation group, respectively.
Human antibody assays indicated that the serum levels of sFRP-4 in HCC patients were significantly higher than those in CHB patients (P<0.05). Additionally, serum sFRP-4 levels were significantly higher in the HCC patients than those in the non-HCC patients in both test group (79.7 vs 41.3 ng/mL; P<0.001) and validation group (89.0 vs 39.0 ng/mL; P<0.001). Areas under the Receiver Operating Characteristic curves (AUCs) for alpha-fetoprotein (AFP) and sFRP-4 were similar in both test group and validation group. In the test group, the combination of sFRP-4 (a sensitivity of 94.4%, a specificity of 60.5% at 46.4 ng/mL) and AFP (a sensitivity of 75.0%, a specificity of 87.2% at 11.3 ng/mL) showed better performance for diagnosing HCC (a sensitivity of 79.2% and a specificity of 95.3%). The AUC for combined sFRP-4 and AFP increased to 0.941 (95% CI: 0.908-0.975), and similar results were seen in the validation group.
sFRP-4 is a candidate serum marker for diagnosing HCC in CHB patients, and the combination of sFRP-4 with AFP may improve the diagnostic accuracy of HCC.
目前用于诊断肝细胞癌（HCC）的方法并不令人满意。在此，我们评估了慢性乙型肝炎（CHB）感染患者血清中分泌型卷曲相关蛋白4（sFRP-4）水平用于诊断HCC的价值。
纳入272例CHB患者，其中142例为HCC患者。招募33名健康受试者作为健康对照。根据入组时间将CHB患者分为测试组和验证组。用人抗体芯片筛选15例患者（8例CHB相关HCC患者，7例CHB患者）的血清标志物。分别在测试组和验证组中评估4种标志物和1种候选标志物。
人抗体检测表明，HCC患者血清sFRP-4水平显著高于CHB患者（P<0.05）。此外，在测试组（79.7 vs 41.3 ng/mL；P<0.001）和验证组（89.0 vs 39.0 ng/mL；P<0.001）中，HCC患者血清sFRP-4水平均显著高于非HCC患者。甲胎蛋白（AFP）和sFRP-4的受试者工作特征曲线下面积（AUC）在测试组和验证组中相似。在测试组中，sFRP-4（在46.4 ng/mL时灵敏度为94.4%，特异性为60.5%）和AFP（在11.3 ng/mL时灵敏度为75.0%，特异性为87.2%）联合使用对HCC的诊断性能更佳（灵敏度为79.2%，特异性为95.3%）。sFRP-4和AFP联合检测的AUC增至0.941（95%CI：0.908 - 0.975），验证组也得到了类似结果。
sFRP-4是诊断CHB患者HCC的候选血清标志物，sFRP-4与AFP联合使用可能提高HCC的诊断准确性。
