Objective: To explore carnosine dipeptidase 1 (CNDP1) potential value as a diagnostic and prognostic evaluator of hepatocellular carcinoma (HCC). Methods: A gene chip and GO analysis were used to screen the candidate marker molecule CNDP1 for HCC diagnosis. 125 cases of HCC cancer tissues, 85 cases of paracancerous tissues, 125 cases of liver cirrhosis tissues, 32 cases of relatively normal liver tissue at the extreme end of hepatic hemangioma, 66 cases from serum samples of HCC, and 82 cases of non-HCC were collected. Real-time fluorescent quantitative PCR, immunohistochemistry, western blot, and enzyme-linked immunosorbent assay were used to detect the differences in mRNA and protein expression levels of CNDP1 in HCC tissue and serum. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival were used to analyze and evaluate the value of CNDP1 in the diagnosis and prognosis of HCC patients. Results: The expression level of CNDP1 was significantly reduced in HCC cancer tissues. The levels of CNDP1 were significantly lower in the cancer tissues and serum of HCC patients than those in liver cirrhosis patients and normal controls. ROC curve analysis showed that the area under the curve of serum CNDP1 in the diagnosis of HCC patients was 0.753 2 (95% CI 0.676-0.830 5), and the sensitivity and specificity were 78.79% and 62.5%, respectively. The combined detection of serum CNDP1 and serum alpha-fetoprotein (AFP) significantly improved the diagnostic accuracy (AUC = 0.820 6, 95% CI 0.753 5-0.887 8). The diagnostic sensitivity and specificity of serum CNDP1 for AFP-negative HCC patients were 73.68% and 68.75% (AUC = 0.793 1, 95% CI 0.708 8-0.877 4), respectively. In addition, the level of serum CNDP1 distinguished small liver cancer (tumor diameter < 3 cm) (AUC = 0.757 1, 95% CI 0.637 4-0.876 8). Kaplan-Meier survival analysis showed that CNDP1 was associated with a poor prognosis in HCC patients. Conclusion: CNDP1 may be a potential biomarker for the diagnostic and prognostic evaluation of HCC, and it has certain complementarity with serum AFP.
目的： 探索肌肽二肽酶（CNDP1）作为肝细胞癌（HCC）诊断和预后评估的潜在价值。 方法： 通过基因芯片及GO分析筛选HCC诊断候选标志分子CNDP1。收集HCC癌组织125例，癌旁组织85例，肝硬化组织125例，肝血管瘤远离部位相对正常肝组织32例，以及66例HCC和82例非HCC患者血清样本。分别采用实时荧光定量PCR、免疫组织化学、蛋白质印迹法和酶联免疫吸附法检测HCC组织及血清CNDP1在mRNA和蛋白表达水平的差异；以受试者操作特征（ROC）曲线和Kaplan-Meier生存分析评估CNDP1在HCC患者诊断和预后中的价值。 结果： CNDP1在HCC癌组织中的表达水平显著降低；在HCC患者癌组织和血清中CNDP1的水平均显著低于肝硬化患者及正常对照。ROC曲线分析显示血清CNDP1诊断HCC患者的曲线下面积为0.753 2（95% CI 0.676~0.830 5），敏感度和特异度分别为78.79% 、62.50%。血清CNDP1与血清甲胎蛋白（AFP）联合检测能较显著提高诊断效能（AUC = 0.820 6，95% CI 0.753 5~0.887 8）。血清CNDP1诊断AFP阴性的HCC患者的敏感度和特异度为73.68%、68.75%（AUC = 0.793 1，95% CI 0.708 8~0.877 4）。此外，血清CNDP1水平能够区分小肝癌（瘤体直径< 3 cm）（AUC = 0.757 1，95% CI 0.637 4~0.876 8）。Kaplan-Meier生存分析显示CNDP1与HCC患者不良预后相关。 结论： CNDP1可能是HCC诊断及预后评估的潜在标志物，并与血清AFP有一定的互补性。.
Keywords: Biomarker; Carnosine dipeptidase 1; Diagnosis; Hepatocellular carcinoma; Prognosis.