Serglycin (SRGN) overexpression predicts poor prognosis in hepatocellular carcinoma patients
Serglycin (SRGN) overexpression predicts poor prognosis in hepatocellular carcinoma patients
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Serglycin (SRGN) 过度表达预示肝细胞癌患者预后不良
DOI：
10.1007/s12032-013-0707-4
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发表时间：
2013-12-01
期刊：
影响因子：
3.4
通讯作者：
Hong, Jian
中科院分区：
文献类型：
--
作者：
He, Lu;Zhou, Xinke;Hong, Jian
肝细胞癌（Hepatocellular carcinoma，HCC）复发率高，预后差，因此寻找新的HCC预测指标并探讨其发生机制是非常必要的。越来越多的证据表明蛋白聚糖丝甘蛋白（SRGN）在肿瘤转移中可能起着至关重要的作用。然而，目前，SRGN在HCC中的功能尚不清楚。在这里，我们评估了SRGN的表达模式，在127个肝癌标本及其邻近的，非肿瘤组织，使用免疫组化检测。我们观察到SRGN在HCC组织中显著上调。在72/127（56.7%）的HCC标本和4/127（3.1%）的邻近非肿瘤组织中可检测到SRGN的表达水平升高（p< 0.001）。进一步相关分析显示，SRGN表达增高与HBV感染、GGT水平、血管浸润、BCLC分期及早期复发呈正相关（p< 0.05）。SRGN表达增加与肝癌患者预后不良相关。在多变量分析中，发现SRGN表达水平是HCC患者总生存期（p= 0.002）和复发时间（p = 0.010）的独立预测因子。此外，SRGN在HCC组织中的表达升高伴随着波形蛋白水平的升高和E-cadherin的缺失。类似地，SRGN表达的减少伴随着E-钙粘蛋白水平的升高和波形蛋白的缺乏。E-cadherin和vimentin是公认的上皮间质转化（EMT）的生物标志物，SRGN的表达可能与EMT相关。我们的研究结果表明，SRGN的表达升高代表了HCC患者的一个重要事件，表明临床结局较差。
Hepatocellular carcinoma (HCC) is known for its high rate of recurrence and poor prognosis, which makes it necessary to identify new predictive markers for HCC and to explore the underlying mechanism(s). Emerging evidence suggests that the proteoglycan serglycin (SRGN) might play a crucial role in tumor metastasis. However, currently, the function of SRGN in HCC remains unknown. Here, we evaluated the expression pattern of SRGN in 127 HCC specimens and their adjacent, non-tumorous tissues using immunohistochemical assays. We observed that SRGN was significantly upregulated in HCC tissues. Elevated expression levels of SRGN were detectable in 72/127 (56.7 %) of the HCC specimens and in 4/127 (3.1 %) of adjacent non-tumorous tissues (p< 0.001). Further correlation analysis demonstrated that the increased expression of SRGN was positively associated with HBV infection, GGT level, vascular invasion, advanced BCLC stage and early recurrence (p< 0.05). Increased SRGN expression correlated with unfavorable prognosis in HCC patients. In multivariate analyses, SRGN expression levels were found to represent an independent predictor for overall survival (p= 0.002) and time to recurrence (p = 0.010) of HCC patients. Furthermore, the elevated expression of SRGN in the HCC tissues was accompanied by elevated levels of vimentin and the absence of E-cadherin. Similarly, the reduced expression of SRGN was accompanied by elevated levels of E-cadherin and the absence of vimentin. E-cadherin and vimentin are well-accepted biomarkers of the epithelial–mesenchymal transition (EMT), and the expression of SRGN might correlate with EMT. Our results demonstrate that the elevated expression of SRGN represents a crucial event in HCC patients that is indicative of poor clinical outcome.