Gatselis Nikolaos K, Zachou Kalliopi, Giannoulis George, Gabeta Stella, Norman Gary L, Dalekos George N
Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, 41110 Larissa, Greece.
Department of Research and Development, Inova Diagnostics, Inc., San Diego, CA 92131, USA.
Cancers (Basel). 2021 Jul 13;13(14):3510. doi: 10.3390/cancers13143510.
The cartilage oligomeric matrix protein (COMP) and Golgi-protein-73 (GP73) have been proposed as markers of liver fibrosis and hepatocellular carcinoma (HCC). Our aim was to assess the performance of the combination of these markers in diagnosing cirrhosis and predicting HCC development. Sera from 288 consecutive patients with chronic liver diseases were investigated by using COMP and GP73-ELISAs. Dual positivity for COMP (>15 U/L) and GP73 (>20 units) was observed in 24 (8.3%) patients, while 30 (10.4%) were GP73(+)/COMP(-), 37/288 (12.8%) GP73(-)/COMP(+), and 197 (68.5%) GP73(-)/COMP(-). Positivity for both markers was associated with cirrhosis [23/24 (95.8%) for GP73(+)/COMP(+) vs. 22/30 (73.3%) for GP73(+)/COMP(-) vs. 25/37 (67.6%) for GP73(-)/COMP(+) vs. 46/197 (23.4%) for GP73(-)/COMP(-); < 0.001]. The combination of GP73, COMP, the aspartate aminotransferase/platelets ratio index, and the Fibrosis-4 score had even higher diagnostic accuracy to detect the presence of cirrhosis [AUC (95% CI): 0.916 (0.878-0.946)] or significant liver fibrosis (METAVIR ≥ F2) [AUC (95% CI): 0.832 (0.768-0.883)] than each marker alone. Kaplan-Meier analysis showed that positivity for both GP73 and COMP was associated with higher rates of HCC development ( < 0.001) and liver-related deaths ( < 0.001) during follow-up. In conclusion, the combination of GP73 and COMP seems efficient to detect cirrhosis and predict worse outcomes and the development of HCC in patients with chronic liver diseases.
软骨寡聚基质蛋白(COMP)和高尔基体蛋白73(GP73)已被提议作为肝纤维化和肝细胞癌(HCC)的标志物。我们的目的是评估这些标志物联合使用在诊断肝硬化和预测HCC发生方面的性能。通过使用COMP和GP73酶联免疫吸附测定法(ELISA)对288例连续的慢性肝病患者的血清进行了研究。在24例(8.3%)患者中观察到COMP(>15 U/L)和GP73(>20单位)双阳性,而30例(10.4%)为GP73(+)/COMP(-),37/288例(12.8%)为GP73(-)/COMP(+),197例(68.5%)为GP73(-)/COMP(-)。两种标志物阳性均与肝硬化相关[GP73(+)/COMP(+)组为23/24(95.8%),GP73(+)/COMP(-)组为22/30(73.3%),GP73(-)/COMP(+)组为25/37(67.6%),GP73(-)/COMP(-)组为46/197(23.4%);P<0.001]。GP73、COMP、天冬氨酸转氨酶/血小板比值指数和Fibrosis-4评分联合使用在检测肝硬化存在[AUC(95%CI):0.916(0.878 - 0.946)]或显著肝纤维化(METAVIR≥F2)[AUC(95%CI):0.832(0.768 - 0.883)]方面比单独使用每个标志物具有更高的诊断准确性。Kaplan-Meier分析表明,在随访期间,GP73和COMP双阳性与更高的HCC发生率(P<0.001)和肝脏相关死亡率(P<0.001)相关。总之,GP73和COMP联合使用似乎能有效地检测肝硬化,并预测慢性肝病患者的不良结局和HCC的发生。