Chen Xinhuang, Liao Yan, Yu Yaqun, Zhu Pengpeng, Li Jun, Qin Liling, Liao Weijia, Huang Zhaoquan
Laboratory of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, P.R. China.
Disease Prevention and Control Center of Guilin, Guilin, Guangxi, P.R. China.
Oncotarget. 2017 Oct 4;8(54):92589-92603. doi: 10.18632/oncotarget.21506. eCollection 2017 Nov 3.
MAP17, a small non-glycosylated membrane protein, was significantly up-regulated in hepatocellular carcinoma (HCC) tissues in our previous genome-wide microarray analysis. In this study, quantitative real-time RT-PCR and immunohistochemistry were applied to examine MAP17 mRNA and protein expression in primary HCC and matched peritumoral tissues. The disease-free survival (DFS) and overall survival (OS) was estimated using the Kaplan-Meier analysis. The expression of MAP17 was significantly higher in HCC tissues compared to the paired peritumoral tissues at both mRNA and protein levels. High MAP17 expression was positively correlated with gender, distant metastasis, early recurrence (≤ 2 year), and serum alpha-fetoprotein (all < 0.05). Kaplan-Meier analysis showed that the DFS ( = 0.004) and OS ( = 0.013) in HCC patients with elevated expression of MAP17 were much worse than that in the low expression subgroup. High level of MAP17 was also significantly associated with a high probability of HCC early recurrence after surgical resection ( = 0.005). Cox regression analysis indicated MAP17 was an independent prognostic factor for DFS (HR, 1.710; 95% CI, 1.156-2.449, = 0.012) and OS (HR, 1.743; 95% CI, 1.152-2.639, = 0.009) in HCC. Silencing MAP17 significantly inhibited the proliferation, invasion and migration of HCC cells , and decreased the expression levels of Akt, p-Akt (Ser473), mTOR, p-mTOR (Ser2448) and MMP-9. Suggesting MAP17 was a novel diagnostic and prognostic biomarker for HCC patients and promoted HCC cell proliferation, invasion and migration via the Akt/mTOR pathway.
在我们之前的全基因组微阵列分析中，小的非糖基化膜蛋白MAP17在肝细胞癌（HCC）组织中显著上调。在本研究中，应用定量实时逆转录PCR和免疫组化检测原发性肝癌及配对癌旁组织中MAP17 mRNA和蛋白表达。采用Kaplan-Meier分析评估无病生存期（DFS）和总生存期（OS）。在mRNA和蛋白水平上，HCC组织中MAP17的表达均显著高于配对的癌旁组织。MAP17高表达与性别、远处转移、早期复发（≤2年）及血清甲胎蛋白呈正相关（均P<0.05）。Kaplan-Meier分析显示，MAP17表达升高的HCC患者的DFS（P=0.004）和OS（P=0.013）比低表达亚组差得多。MAP17高水平也与手术切除后HCC早期复发的高概率显著相关（P=0.005）。Cox回归分析表明，MAP17是HCC患者DFS（风险比[HR]，1.710；95%可信区间[CI]，1.156-2.449，P=0.012）和OS（HR，1.743；95%CI，1.152-2.639，P=0.009）的独立预后因素。沉默MAP17可显著抑制HCC细胞的增殖、侵袭和迁移，并降低Akt、p-Akt（Ser473）、mTOR、p-mTOR（Ser2448）和MMP-9的表达水平。提示MAP17是HCC患者一种新的诊断和预后生物标志物，并通过Akt/mTOR途径促进HCC细胞增殖、侵袭和迁移。
