Zhuang Liping, Xu Litao, Wang Peng, Meng Zhiqiang
Department of Integrative Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
PLoS One. 2015 Feb 2;10(2):e0117274. doi: 10.1371/journal.pone.0117274. eCollection 2015.
Circulating miRNAs are promising biomarkers for predicting the aggressiveness of hepatocellular carcinoma (HCC). We aimed to identify differentially expressed miRNAs in the serum of HCC patients with different Barcelona Clinic Liver Cancer (BCLC) stage, and to investigate the potential of serum miRNAs as biomarkers for patient outcomes. In the discovery stage, TaqMan Low-Density Array was used to test the difference in levels of serum miRNAs between 20 patients with portal vein tumor thrombosis (PVTT) and 20 patients without PVTT. The detected serum miRNAs then were validated in 182 patients. Fifteen serum miRNAs showed more than two-fold higher expression in patients with PVTT, and miR-128-2 was found to be significantly up-regulated and was selected for further validation. In the validation stage, patients were divided into two groups with low or high serum miR-128-2 using the median expression level of all 182 cases as the cut-off point. Kaplan-Meier analysis revealed that patients with low level of serum miR-128-2 had favorable trends of survival (log rank = 13.031, p < 0.001). The median survivals for patients with a low and high level of serum miR-128-2 were 625 (95% CI, 527-722) days and 426 (95% CI, 362-491) days, respectively. MiR-128-2 was also an independent factor of overall survival (p = 0.001, HR 2.793, 95%CI 1.550, 5.033). Serum levels of the ubiquitously expressed miR-128-2 showed no significant correlation with parameters of liver damage or liver function. In addition, expressions of miR-128-2 in HCC tissues were up-regulated in comparison with adjacent non-tumor tissues. In conclusion, serum level of miR-128-2 serves as a noninvasive biomarker for the overall survival of patients with hepatocellular carcinoma.
循环微小RNA（miRNA）是预测肝细胞癌（HCC）侵袭性的有前景的生物标志物。我们旨在鉴定不同巴塞罗那临床肝癌（BCLC）分期的HCC患者血清中差异表达的miRNA，并研究血清miRNA作为患者预后生物标志物的潜力。在发现阶段，使用TaqMan低密度阵列检测20例门静脉肿瘤血栓形成（PVTT）患者和20例无PVTT患者血清miRNA水平的差异。然后在182例患者中对检测到的血清miRNA进行验证。15种血清miRNA在PVTT患者中的表达高出两倍以上，并且发现miR-128-2显著上调并被选作进一步验证。在验证阶段，以所有182例病例的中位表达水平为分界点，将患者分为血清miR-128-2水平低或高的两组。Kaplan-Meier分析显示，血清miR-128-2水平低的患者有良好的生存趋势（对数秩=13.031，p<0.001）。血清miR-128-2水平低和高的患者的中位生存期分别为625（95%CI，527-722）天和426（95%CI，362-491）天。MiR-128-2也是总生存期的独立因素（p=0.001，HR 2.793，95%CI 1.550，5.033）。普遍表达的miR-128-2的血清水平与肝损伤或肝功能参数无显著相关性。此外，与相邻非肿瘤组织相比，HCC组织中miR-128-2的表达上调。总之，血清miR-128-2水平可作为肝细胞癌患者总生存期的非侵入性生物标志物。
