Lorente Leonardo, Rodriguez Sergio T, Sanz Pablo, Pérez-Cejas Antonia, Padilla Javier, Díaz Dácil, González Antonio, Martín María M, Jiménez Alejandro, Barrera Manuel A
Intensive Care Unit, Hospital Universitario de Canarias, Ofra, s/n. La Laguna, Tenerife 38320, Spain.
Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Crta Rosario s/n, Santa Cruz Tenerife 38010, Spain.
Int J Mol Sci. 2016 Sep 9;17(9):1524. doi: 10.3390/ijms17091524.
Cytokeratin (CK)-18 is the major intermediate filament protein in the liver and during hepatocyte apoptosis is cleaved by the action of caspases; the resulting fragments are released into the blood as caspase-cleaved cytokeratin (CCCK)-18. Higher circulating levels of CCCK-18 have been found in patients with hepatocellular carcinoma (HCC) than in healthy controls and than in cirrhotic patients. However, it is unknown whether serum CCCK-18 levels before liver transplantation (LT) in patients with HCC could be used as a prognostic biomarker of one-year survival, and this was the objective of our study with 135 patients. At one year after LT, non-survivors showed higher serum CCCK-18 levels than survivors (p = 0.001). On binary logistic regression analysis, serum CCCK-18 levels >384 U/L were associated with death at one year (odds ratio = 19.801; 95% confidence interval = 5.301-73.972; p < 0.001) after controlling for deceased donor age. The area under the receiver operating characteristic (ROC) curve of serum CCCK-18 levels to predict death at one year was 77% (95% CI = 69%-84%; p < 0.001). The new finding of our study was that serum levels of CCCK-18 before LT in patients with HCC could be used as prognostic biomarker of survival.
细胞角蛋白（CK）-18是肝脏中的主要中间丝蛋白，在肝细胞凋亡过程中会被半胱天冬酶切割；产生的片段会作为半胱天冬酶切割的细胞角蛋白（CCCK）-18释放到血液中。肝细胞癌（HCC）患者的循环CCCK-18水平高于健康对照者和肝硬化患者。然而，HCC患者肝移植（LT）前的血清CCCK-18水平是否可作为一年生存率的预后生物标志物尚不清楚，这也是我们对135例患者进行研究的目的。LT术后一年，非存活者的血清CCCK-18水平高于存活者（p = 0.001）。在二元逻辑回归分析中，在控制供体死亡年龄后，血清CCCK-18水平>384 U/L与一年时的死亡相关（比值比 = 19.801；95%置信区间 = 5.301 - 73.972；p < 0.001）。血清CCCK-18水平预测一年死亡的受试者工作特征（ROC）曲线下面积为77%（95% CI = 69% - 84%；p < 0.001）。我们研究的新发现是，HCC患者LT前的血清CCCK-18水平可作为生存的预后生物标志物。
