Prognostic impact of SET domain-containing protein 8 and protein arginine methyltransferase 5 in patients with hepatocellular carcinoma following curative resection.
Prognostic impact of SET domain-containing protein 8 and protein arginine methyltransferase 5 in patients with hepatocellular carcinoma following curative resection.
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含SET结构域的蛋白8和蛋白精氨酸甲基转移酶5对肝细胞癌根治性切除术后患者预后的影响
DOI：
10.3892/ol.2018.9083
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发表时间：
2018-09
期刊：
影响因子：
2.9
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Lin Z;Jia H;Hong L;Zheng Y;Shao W;Ren X;Zhu W;Lu L;Lu M;Zhang J;Chen J
组蛋白甲基转移酶是肝细胞癌 (HCC) 发生和进展的重要决定因素，也是有前景的治疗靶点。然而，多种组蛋白甲基转移酶的表达谱是否代表较差的预后尚不清楚。本研究的目的是探讨组蛋白甲基化与 HCC 表型之间的关联，以及将含有 SET 结构域的蛋白 8 (SET8) 与蛋白精氨酸甲基转移酶 5 (PRMT5) 的表达水平相结合，对治愈性切除后 HCC 患者的预后价值。这项回顾性研究包括 195 名因 HCC 接受肝切除术的连续患者。在石蜡包埋的肿瘤组织微阵列上进行 SET8 和 PRMT5 的免疫组织化学染色。通过单变量和多变量分析，分析表达与临床病理学特征、标志物共表达和患者生存的相关性。 104 名患者 (53.3%) 出现 SET8 阳性表达，并且与 PRMT5 表达相关 (n=106, 54.4%, P<0.05)。免疫组织化学分析表明，SET8 和 PRMT5 的高表达与较差的总生存期（OS，P<0.001）和复发时间（TTR，P<0.001）显着相关。多变量 Cox 分析显示，SET8 和 PRMT5 以及血管侵犯、肿瘤大小和肿瘤数量是 OS 和 TTR 的独立预后因素。 SET8 和 PRMT5 的组合显示出预测患者死亡率和疾病复发的能力有所提高（分别为 P=0.002 和 P=0.004），特别是对于早期复发的预测（P<0.001）。总之，SET8联合PRMT5的高表达与HCC患者的高复发率和低生存率相关。组蛋白甲基化的独立模式代表了对肿瘤进展和 HCC 治疗靶点的新见解。
Histone methyltransferases are important determinants of the initiation and progression of hepatocellular carcinoma (HCC) and represent promising therapeutic targets. However, whether the expression profile of multiple histone methyltransferases represents a poorer prognosis is entirely unknown. The aim of the present study was to investigate the association between histone methylation and HCC phenotype, and the prognostic value of combining expression levels of SET domain-containing protein 8 (SET8) with protein arginine methyltransferase 5 (PRMT5) in patients with HCC following curative resection. The retrospective study included 195 consecutive patients who had undergone hepatectomy for HCC. Immunohistochemical staining for SET8 and PRMT5 was performed on paraffin-embedded tumor tissue microarrays. Expression was analyzed for correlations with clinicopathological features, marker co-expression and patients' survival by univariate and multivariate analyses. Positive SET8 expression was noted in 104 patients (53.3%), and was associated with PRMT5 expression (n=106, 54.4%, P<0.05). Immunohistochemical analysis demonstrated that high expression of SET8 and PRMT5 was significantly associated with poor overall survival (OS, P<0.001) and time to recurrence (TTR, P<0.001). Multivariate Cox analysis revealed that SET8 and PRMT5, along with vascular invasion, tumor size and tumor number, were independent prognostic factors for OS and TTR. The combination of SET8 and PRMT5 demonstrated an improved capacity to predict patient mortality and disease recurrence (P=0.002 and P=0.004, respectively), particularly for the prediction of early recurrence (P<0.001). In conclusion, high expression of SET8 combined with PRMT5 was associated with a high rate of recurrence and poor survival in patients with HCC. The independent pattern of histone methylation represents a novel insight into tumor progression and therapeutic targets for HCC.
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