LRG1 expression indicates unfavorable clinical outcome in hepatocellular carcinoma.
LRG1 expression indicates unfavorable clinical outcome in hepatocellular carcinoma.
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LRG1 表达表明肝细胞癌的临床结果不佳。
DOI：
10.18632/oncotarget.5967
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发表时间：
2015-12-08
期刊：
影响因子：
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通讯作者：
Yun JP
中科院分区：
文献类型：
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作者：
Wang CH;Li M;Liu LL;Zhou RY;Fu J;Zhang CZ;Yun JP
富含亮氨酸的α-2-糖蛋白1（Leucine-rich-alpha-2-glycoprotein 1，LRG 1）是一种新的癌基因相关蛋白，与人类肿瘤的发生发展密切相关，但其在肝细胞癌（hepatocellular carcinoma，HCC）中的作用尚不清楚。在这里，我们发现LRG 1的表达在HCC组织中显著增加，与非肿瘤组织相比。LRG 1高表达与肿瘤大小（P = 0.004）、分化程度（P = 0.010）、TNM分期（P < 0.001）和血管浸润（P = 0.019）有关。Kaplan-Meier分析显示，在474例HCC患者的训练队列中，LRG 1表达与总生存期和无病生存期密切相关。在303例HCC患者的独立队列中进一步验证了相关性。分层生存分析证实了LRG 1的预后意义。多因素考克斯回归分析显示，LRG 1是影响肝癌患者总生存期（危险比= 1.582，95%可信区间：1.345-1.862，P < 0.001）和无病生存期（危险比= 1.280，95%可信区间：1.037-1.581，P = 0.022）的独立预后不良指标。体外实验结果表明，LRG 1能显著促进细胞迁移，但对细胞增殖无影响。总的来说，我们的数据显示LRG 1显著上调，并作为HCC预后不良的独立因素。因此，我们的研究提供了一个有前途的生物标志物的预后预测肝癌的临床管理。
Leucine-rich-alpha-2-glycoprotein1 (LRG1) is a novel oncogene-associated protein which has been clarified vital to the progression of human cancers, but its role in hepatocellular carcinoma (HCC) remains unclear. Here, we showed that the expression of LRG1 was noticeably increased in HCC tissues, compared to the nontumorous tissues. High LRG1 expression was significantly associated with tumor size (P = 0.004), tumor differentiation (P = 0.010), TNM stage (P < 0.001) and vascular invasion (P = 0.019). Kaplan-Meier analysis showed that LRG1 expression was closely correlated to overall survival and disease-free survival in a training cohort of 474 patients with HCC. The correlation was further validated in an independent cohort of 303 HCC patients. The prognostic implication of LRG1 was confirmed by stratified survival analyses. Multivariate Cox regression model indicated LRG1 as an independent poor prognostic indicator for overall survival (Hazard ratio = 1.582, 95% confident interval: 1.345–1.862, P < 0.001) and disease-free survival (Hazard ratio = 1.280, 95% confident interval: 1.037–1.581, P = 0.022) in HCC. In vitro data showed that LRG1 markedly promoted cell migration but has no effect on cell proliferation. Collectively, our data show that LRG1 is markedly up-regulated and serves as an independent factor of poor outcomes in HCC. Our study therefore provides a promising biomarker for prognostic prediction in clinical management of HCC.