Bağırsakçı Ezgi, Şahin Eren, Atabey Neşe, Erdal Esra, Guerra Vito, Carr Brian I
Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir, Turkey.
Oncology. 2017;93(2):136-142. doi: 10.1159/000471807. Epub 2017 May 10.
Levels of serum albumin have recently emerged, together with C-reactive protein, as an important prognostic indicator for hepatocellular carcinoma (HCC). It has recently been reported that larger HCCs are associated with lower albumin levels. However, the albumin-mediated growth decrease has yet to be determined.
We examined a large HCC cohort and then by direct exposure of HCC cells in vitro, the relationship of albumin levels to HCC growth.
We found that patients with lower albumin levels had significantly larger maximum tumor diameters, more portal vein thrombosis, more tumor multifocality, higher α-fetoprotein levels, and a lower survival than patients with higher albumin levels. Direct addition of exogenous albumin at physiological concentrations resulted in decreased growth in several HCC cell lines in vitro. We found a decrease in MAP kinase levels and in levels of Cdk2 and Cdk4, cyclinE, as well as in α-fetoprotein.
These results indicate that in addition to its role as a monitor of systemic inflammation, albumin may have a direct role in HCC growth inhibition, either through modulation of α-fetoprotein or through its actions on growth-controlling kinases.
血清白蛋白水平最近与C反应蛋白一起，成为肝细胞癌（HCC）的重要预后指标。最近有报道称，较大的肝癌与较低的白蛋白水平相关。然而，白蛋白介导的生长抑制作用尚未确定。
我们研究了一个大型肝癌队列，然后通过体外直接暴露肝癌细胞，研究白蛋白水平与肝癌生长的关系。
我们发现，白蛋白水平较低的患者与白蛋白水平较高的患者相比，最大肿瘤直径明显更大，门静脉血栓形成更多，肿瘤多灶性更多，甲胎蛋白水平更高，生存率更低。在生理浓度下直接添加外源性白蛋白导致几种肝癌细胞系在体外生长减少。我们发现丝裂原活化蛋白激酶水平以及细胞周期蛋白依赖性激酶2（Cdk2）、细胞周期蛋白依赖性激酶4（Cdk4）、细胞周期蛋白E以及甲胎蛋白水平均下降。
这些结果表明，除了作为全身炎症的监测指标外，白蛋白可能通过调节甲胎蛋白或通过其对生长控制激酶的作用，在肝癌生长抑制中发挥直接作用。
