Expression of variant isoforms of the tyrosine kinase SYK determines the prognosis of hepatocellular carcinoma.
Expression of variant isoforms of the tyrosine kinase SYK determines the prognosis of hepatocellular carcinoma.
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DOI：
10.1158/0008-5472.can-13-2104
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发表时间：
2014-03-15
期刊：
影响因子：
11.2
通讯作者：
Chung RT
中科院分区：
文献类型：
--
作者：
Hong J;Yuan Y;Wang J;Liao Y;Zou R;Zhu C;Li B;Liang Y;Huang P;Wang Z;Lin W;Zeng Y;Dai JL;Chung RT
酪氨酸激酶SYK已被报道为人类肝细胞癌（HCC）的一种新的生物标志物，但其两个亚型SYK(L)和SYK(S)的功能贡献尚不明确。在这项研究中，我们探讨了它们在HCC中的生物学功能和可能的预后价值。SYK(L)在38%的HCC检测的人类标本中下调，而SYK(S)在40%的这些标本中可检测到，但在没有肝硬化的正常肝组织样本中未检测到。SYK(S)表达与肿瘤转移特征的病理参数相关，包括多发肿瘤（P = 0.003）和血管侵犯（P = 0.001）。此外，SYK(S)在HCC标本中与上皮-间质转化（EMT）特异性相关。功能研究表明，SYK(S)通过ERK途径促进肿瘤生长，抑制细胞凋亡，诱导EMT，与SYK(L)相反。SYK（L+/S−）肿瘤患者比SYK（L−/S−）或SYK（L+/S+）肿瘤患者的总生存期和复发时间更长（P < 0.001）。综上所述，我们的研究结果表明，SYK(S)增强了肝癌的侵袭，而SYK(L)抑制了肝癌的转移。我们认为SYK(L)下调或SYK(S)升高是HCC患者生存不良的有力预测因子，表明需要积极的治疗干预。
The tyrosine kinase SYK has been reported as a novel biomarker for human hepatocellular carcinoma (HCC), but the functional contributions of its two isoforms SYK(L) and SYK(S) are undefined. In this study, we investigated their biologic functions and possible prognostic values in HCC. SYK(L) was downregulated in 38% of human specimens of HCC examined, whereas SYK(S) was detectable in 40% of these specimens but not in normal liver tissue samples without cirrhosis. SYK(S) expression correlated with pathological parameters characteristic of tumor metastasis, including multiple tumors (P = 0.003) and vascular invasion (P = 0.001). Further, SYK(S) was specifically associated with epithelial-mesenchymal transition (EMT) in HCC specimens. Functional studies showed that SYK(S) promoted tumor growth, suppressed apoptosis and induced EMT through the ERK pathway, countering the opposite effects of SYK(L). Patients with SYK(L+/S−) tumors exhibited longer overall survival and time to recurrence than those with SYK(L−/S−) or SYK(L+/S+) tumors (P < 0.001). Taken together, our findings showed that SYK(S) enhances invasion whereas SYK(L) inhibits metastasis in HCC. We suggest that SYK(L) downregulation or SYK(S) elevation are strong predictors of poor survival in HCC patients, indicative of a need for aggressive therapeutic intervention.