Decreased expression of PBLD correlates with poor prognosis and functions as a tumor suppressor in human hepatocellular carcinoma.
Decreased expression of PBLD correlates with poor prognosis and functions as a tumor suppressor in human hepatocellular carcinoma.
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PBLD 表达的降低与不良预后相关，并在人肝细胞癌中充当肿瘤抑制因子。
DOI：
10.18632/oncotarget.6358
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发表时间：
2016-01-05
期刊：
影响因子：
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通讯作者：
Nie Y
中科院分区：
文献类型：
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作者：
Li A;Yan Q;Zhao X;Zhong J;Yang H;Feng Z;Du Y;Wang Y;Wang Z;Wang H;Zhou Y;Liu S;Nie Y
最近积累的基因组和蛋白质组学数据表明，吩嗪生物合成样结构域蛋白（PBLD）的表达减少经常参与肝细胞癌（HCC）。然而，目前对其表达模式、临床意义和生物学功能缺乏系统的研究。在这里，我们发现PBLD在HCC组织中相对于邻近的非致瘤性肝组织经常降低。这种表达降低与肿瘤分化差和晚期肿瘤阶段显著相关。Kaplan-Meier分析进一步显示，PBLD低表达患者的无复发生存期和总生存期显著更差。此外，多变量分析显示PBLD是OS和RFS的独立预测因子。在另一个独立队列中进一步验证了PBLD的预后价值。我们还发现PBLD在体外抑制HCC细胞的生长和侵袭，在体内抑制肿瘤的生长。此外，PBLD的强制表达影响了MAPK、NF-κB、EMT和血管生成信号通路相关的多个下游基因。PBLD缺失是HCC患者预后不良的独立预测因子。PBLD表达升高可能通过灭活几种肿瘤发生相关的信号通路来降低HCC细胞的生长和侵袭。
Recent accumulating genomic and proteomic data suggested that decreased expression of phenazine biosynthesis-like domain-containing protein (PBLD) was frequently involved in hepatocellular carcinoma (HCC). However, there is lack of systematical investigation focusing on its expression pattern, clinical relevance, and biological function. Here, we found that PBLD was frequently decreased in HCC tissues relative to adjacent non-tumorigenic liver tissues. This decreased expression was significantly associated with poor tumor differentiation and advanced tumor stage. Kaplan–Meier analysis further showed that recurrence-free survival and overall survival were significantly worse among patients with low PBLD expression. Moreover, multivariate analyses revealed that PBLD was an independent predictor of OS and RFS. This prognostic value of PBLD was further validated in another independent cohort. We also found PBLD inhibited HCC cell growth and invasion in vitro and tumor growth in vivo. Furthermore, forced expression of PBLD influenced multiple downstream genes related to MAPK, NF-κB, EMT, and angiogenesis signaling pathways. PBLD deletion was an independent predictor of poor prognosis in patients with HCC. Elevated PBLD expression may reduce HCC cell growth and invasion via inactivation of several tumorigenesis-related signaling pathways.