Long non-coding RNAs (lncRNAs) are often aberrantly expressed in Hepatocellular Carcinoma (HCC). We hypothesize that lncRNAs modulate HCC prognoses through differential deregulation of key lncRNAs affecting important gene network in key cancer pathways associated with pertinent clinical phenotype. Here, we present a novel approach integrating lncRNA-mRNA expression profiles with clinical characteristics to identify lncRNA signatures in clinically-relevant co-expression lncRNA-mRNA networks residing in pertinent cancer pathways. Notably one network, associated with poorer prognosis, comprises five up-regulated lncRNAs significantly correlated (|Pearson Correlation Coefficient|≥ 0.9) with 91 up-regulated genes in the cell-cycle and Rho-GTPase pathways. All 5 lncRNAs and 85/91 (93.4%) of the correlated genes were significantly associated with higher tumor-grade while 3/5 lncRNAs were also associated with no tumor capsule. Interestingly, 2/5 lncRNAs that are correlated with numerous genes in this oncogenic network were experimentally shown to up-regulate genes involved in cell-cycle and transcriptional regulation. Another network comprising 4 down-regulated lncRNAs and 8 down-regulated metallothionein-family genes are significantly associated with tumor invasion. The identification of these key lncRNAs signatures that deregulate important network of genes in key cancer pathways associated with pertinent clinical phenotype may facilitate the design of novel therapeutic strategies targeting these ‘master’ regulators for better patient outcome.

长非编码RNA（lncRNA）通常在肝细胞癌（HCC）中异常表达。我们假设，lncRNAs通过对影响相关临床表型的关键癌症途径中重要基因网络的关键lncRNA的差异去调节来调节HCC预后。在这里，我们提出了一种新颖的方法，将具有临床特征的lncRNA-mRNA表达谱与临床特征相结合，以鉴定位于相关癌症途径中的临床相关共表达lncRNA-mRNA网络中的lncRNA签名。值得注意的是，一个与预后较差有关的网络包含五个上调的lncRNA，它们与细胞周期和Rho-GTPase途径中的91个上调基因显着相关（| Pearson相关系数|≥0.9）。所有5个lncRNA和85/91（93。4％的相关基因与较高的肿瘤等级显着相关，而3/5 lncRNA也与无肿瘤包膜相关。有趣的是，实验证明与该致癌网络中众多基因相关的2/5 lncRNA可以上调参与细胞周期和转录调控的基因。包含4个下调的lncRNA和8个下调的金属硫蛋白家族基因的另一个网络与肿瘤浸润显着相关。对这些关键lncRNAs信号的识别可以使与相关临床表型相关的关键癌症途径中的重要基因网络失控，从而可以促进针对这些“主要”调节子的新型治疗策略的设计，从而改善患者的治疗效果。有趣的是，实验证明与该致癌网络中众多基因相关的2/5 lncRNA可以上调参与细胞周期和转录调控的基因。包含4个下调的lncRNA和8个下调的金属硫蛋白家族基因的另一个网络与肿瘤浸润显着相关。对这些关键lncRNAs信号的识别可以使与相关临床表型相关的关键癌症途径中的重要基因网络失控，从而有助于设计针对这些“主要”调节子的新型治疗策略，以改善患者的预后。有趣的是，实验证明与该致癌网络中众多基因相关的2/5 lncRNA可以上调参与细胞周期和转录调控的基因。包含4个下调的lncRNA和8个下调的金属硫蛋白家族基因的另一个网络与肿瘤浸润显着相关。对这些关键lncRNAs信号的识别可以使与相关临床表型相关的关键癌症途径中的重要基因网络失控，从而有助于设计针对这些“主要”调节子的新型治疗策略，以改善患者的预后。包含4个下调的lncRNA和8个下调的金属硫蛋白家族基因的另一个网络与肿瘤浸润显着相关。对这些关键lncRNAs信号的识别可以使与相关临床表型相关的关键癌症途径中的重要基因网络失控，从而有助于设计针对这些“主要”调节子的新型治疗策略，以改善患者的预后。包含4个下调的lncRNA和8个下调的金属硫蛋白家族基因的另一个网络与肿瘤浸润显着相关。对这些关键lncRNAs信号的识别可以使与相关临床表型相关的关键癌症途径中的重要基因网络失控，从而有助于设计针对这些“主要”调节子的新型治疗策略，以改善患者的预后。