Department of Clinical Laboratory, Cancer Hospital of Guangxi Medical University, Nanning 530021, Guangxi, PR China; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China.
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, PR China.
Clin Res Hepatol Gastroenterol. 2021 Sep;45(5):101583. doi: 10.1016/j.clinre.2020.11.013. Epub 2021 Mar 21.
α-fetoprotein is often used in the diagnosis of hepatocellular carcinoma (HCC). However, there are currently less efficient and highly specific biomarkers to distinguish AFP-negative HCC from liver cirrhosis (LC) patients.
We retrospectively analyzed the data of patients who were treated in our hospitals. iTRAQ coupled with mass spectrometry was used to identify candidate serum proteins in a discovery set (n = 36) including AFP-negative HCC and LC patients. After Western blot detection, potential serum biomarkers were confirmed using ELISA in a validation set (n = 90). The diagnostic performance of the selected proteins was assessed using receiver operating characteristic (ROC).
PON1 and ATIII were selected as target proteins and were significantly higher in LC than those in AFP-negative HCC patients as validated by Western blot and ELISA, which was consistent with the result of iTRAQ. The AUC was 0.848 as PON1 and ATIII were combined (sensitivity: 80.0%; specificity: 73.3%), and performed much better than that of a single biomarker.
These findings suggest that PON1 and ATIII have the potential to serve as effective biomarkers for distinguishing AFP-negative HCC from cirrhosis.
甲胎蛋白常用于肝细胞癌（HCC）的诊断。然而，目前尚无更有效和高度特异性的生物标志物来区分 AFP 阴性 HCC 与肝硬化（LC）患者。
我们对在我院治疗的患者进行了回顾性分析。在包含 AFP 阴性 HCC 和 LC 患者的发现集（n=36）中，采用 iTRAQ 联合质谱技术鉴定候选血清蛋白。在验证集（n=90）中，Western blot 检测后，使用 ELISA 对潜在的血清生物标志物进行了确认。使用受试者工作特征（ROC）评估所选蛋白的诊断性能。
PON1 和 ATIII 被选为目标蛋白，Western blot 和 ELISA 验证显示，LC 患者的 PON1 和 ATIII 明显高于 AFP 阴性 HCC 患者，与 iTRAQ 的结果一致。PON1 和 ATIII 联合的 AUC 为 0.848（灵敏度：80.0%；特异性：73.3%），优于单一生物标志物。
这些发现表明，PON1 和 ATIII 有可能成为区分 AFP 阴性 HCC 与肝硬化的有效生物标志物。
