Evaluation of Fucosylated Haptoglobin and Mac-2 Binding Protein as Serum Biomarkers to Estimate Liver Fibrosis in Patients with Chronic Hepatitis C.
Evaluation of Fucosylated Haptoglobin and Mac-2 Binding Protein as Serum Biomarkers to Estimate Liver Fibrosis in Patients with Chronic Hepatitis C.
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DOI：
10.1371/journal.pone.0151828
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Takehara T
中科院分区：
文献类型：
--
作者：
Tawara S;Tatsumi T;Iio S;Kobayashi I;Shigekawa M;Hikita H;Sakamori R;Hiramatsu N;Miyoshi E;Takehara T
根据糖蛋白质组分析的结果，岩藻糖化结合珠蛋白(Fuc-HPT)和Mac-2结合蛋白(Mac-2 BP)被鉴定为癌症生物标志物。最近，我们报道了这些糖生物标志物与非酒精性脂肪性肝病(NAFLD)患者的肝纤维化和/或肝细胞膨胀有关。我们评估了这些糖蛋白在317例慢性丙型肝炎患者中评估肝纤维化的能力。我们分别用凝集素抗体酶联免疫吸附试验和酶联免疫吸附试验测定了血清Fuc-HPT和Mac-2BP水平。血清Fuc-HPT和Mac-2BP水平均随肝纤维化进展而升高。多因素分析显示Mac-2BP是与中度肝纤维化相关的独立因素(F≥2)。相比之下，Fuc-HPT是与晚期肝纤维化相关的独立因素(F≥3)。在评估肝纤维化方面，这些糖标记物的水平与著名的肝纤维化指标相关，如天冬氨酸氨基转移酶/血小板比率指数(APRI)和纤维化-4(FIB4)指数。APRI或FIB4指数与Fuc-HPT或Mac-2 BP水平联合检测可增加诊断肝纤维化的AUC值。有趣的是，在血清Fuc-HPT和Mac-2BP水平升高的患者中，肝细胞癌的累积发病率显著更高。结论：Fuc-HPT和Mac-2BP均可作为慢性丙型肝炎患者肝纤维化的糖类生物标志物和肝细胞癌的预测指标。
Fucosylated haptoglobin (Fuc-Hpt) and Mac-2 binding protein (Mac-2 bp) are identified as cancer biomarkers, based on the results from a glyco-proteomic analysis. Recently, we reported that these glyco-biomarkers were associated with liver fibrosis and/or ballooning hepatocytes in patients with nonalcoholic fatty liver disease (NAFLD). We evaluated the ability of these glycoproteins to estimate liver fibrosis in 317 patients with chronic hepatitis C. We measured the serum Fuc-Hpt and Mac-2 bp levels using a lectin-antibody ELISA and ELISA, respectively. The serum levels of both Fuc-Hpt and Mac-2 bp increased with the progression of liver fibrosis. The multivariate analysis revealed that Mac-2 bp was an independent factor associated with moderate liver fibrosis (F ≥ 2). In contrast, Fuc-Hpt was an independent factor associated with advanced liver fibrosis (F ≥ 3). In terms of evaluating liver fibrosis, the serum levels of these glycomarkers were correlated with well-known liver fibrosis indexes, such as the aspartate aminotransferase to platelet ratio index (APRI) and Fibrosis-4 (FIB4) index. An assay that combined the APRI or FIB4 index and the Fuc-Hpt or Mac-2 bp levels increased the AUC value for diagnosing hepatic fibrosis. Interestingly, the cumulative incidence of hepatocellular carcinoma (HCC) was significantly higher in the patients with elevated serum levels of Fuc-Hpt and Mac-2 bp. In conclusion, both Fuc-Hpt and Mac-2 bp could be useful glyco-biomarkers of liver fibrosis and predictors of HCC in patients with chronic hepatitis C.