302 Hospital of PLA, Beijing 100039, China.
302 Hospital of PLA, Beijing 100039, China.
Cancer Epidemiol. 2014 Aug;38(4):408-13. doi: 10.1016/j.canep.2014.05.001. Epub 2014 Jun 10.
Previous evidence has shown that microRNA (miR)-224 may function as an onco-miRNA in hepatocellular carcinoma (HCC) cells by activating AKT signaling. However, little is known about the clinical significance of the combined expression of miR-224 and phosphorylated-AKT (pAKT) on human HCC. The aim of this study was to investigate the synergistical influence of miR-224 and pAKT on clinical characteristics and prognosis in patients with HCC.
One-hundred and thirty HCC patients who had undergone curative liver resection were selected. In situ hybridization and immunohistochemistry were respectively performed to detect the expression of miR-224 and pAKT in the respective tumors.
Compared with the adjacent nonneoplastic liver tissues, the expression levels of miR-224 and pAKT protein in HCC tissues were both significantly increased (both P<0.001). In addition, the combined upregulation of miR-224 and pAKT protein was significantly associated with serum AFP (P=0.01), tumor stage (P=0.002) and tumor grade (P=0.008). Moreover, HCC patients highly expressing both miR-224 and pAKT protein had worse 5-year disease-free survival and 5-year overall survival (both P<0.001). Furthermore, the Cox proportional hazards model showed that the combined upregulation of miR-224 and pAKT protein (miR-224-high/pAKT-high) may be independent poor prognostic factors for both 5-year disease-free survival (P=0.008) and 5-year overall survival (P=0.01) in HCC.
These results indicate for the first time that miR-224 upregulation and AKT activation may synergistically associate with tumor progression of HCC. The combined high expression of miR-224 and pAKT may be a potential indicator for predicting unfavorable prognosis in HCC patients.
既往研究表明，微小 RNA（miR）-224 可能通过激活 AKT 信号通路在肝癌（HCC）细胞中发挥致癌 miRNA 的作用。然而，miR-224 与磷酸化 AKT（pAKT）在人 HCC 中的联合表达的临床意义尚不清楚。本研究旨在探讨 miR-224 与 pAKT 的联合表达对 HCC 患者临床特征和预后的协同影响。
选择 130 例接受根治性肝切除术的 HCC 患者。分别采用原位杂交和免疫组化检测各自肿瘤中 miR-224 和 pAKT 蛋白的表达。
与相邻非肿瘤性肝组织相比，HCC 组织中 miR-224 和 pAKT 蛋白的表达水平均显著升高（均 P<0.001）。此外，miR-224 和 pAKT 蛋白的联合上调与血清 AFP（P=0.01）、肿瘤分期（P=0.002）和肿瘤分级（P=0.008）显著相关。此外，高表达 miR-224 和 pAKT 蛋白的 HCC 患者 5 年无病生存率和 5 年总生存率均较差（均 P<0.001）。此外，Cox 比例风险模型显示，miR-224 和 pAKT 蛋白的联合上调（miR-224-高/pAKT-高）可能是 HCC 患者 5 年无病生存率（P=0.008）和 5 年总生存率（P=0.01）的独立不良预后因素。
这些结果首次表明，miR-224 的上调和 AKT 的激活可能协同与 HCC 的肿瘤进展相关。miR-224 和 pAKT 的联合高表达可能是预测 HCC 患者不良预后的潜在指标。
