Prognostic impact of SET domain‑containing protein 8 and protein arginine methyltransferase 5 in patients with hepatocellular carcinoma following curative resection

Lin,Zhifei; Jia,Huliang; Hong,Liang; Zheng,Yahui; Shao,Weiqin; Ren,Xudong; Zhu,Wenwei; Lu,Lu; Lu,Ming; Zhang,Jubo; Chen,Jinhong

doi:10.3892/ol.2018.9083

Prognostic impact of SET domain‑containing protein 8 and protein arginine methyltransferase 5 in patients with hepatocellular carcinoma following curative resection

Authors:
- Zhifei Lin
- Huliang Jia
- Liang Hong
- Yahui Zheng
- Weiqin Shao
- Xudong Ren
- Wenwei Zhu
- Lu Lu
- Ming Lu
- Jubo Zhang
- Jinhong Chen
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Affiliations: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Infectious Diseases, Ruian People's Hospital, Wenzhou, Zhejiang 325200, P.R. China, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China
Published online on: July 5, 2018 https://doi.org/10.3892/ol.2018.9083
Pages: 3665-3673
Copyright: © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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