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

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.

SE translation mRNA overexpression: a potential prognostic predictor in breast cancer

“…Moreover, SET mRNA overexpression could act as a poor prognostic factor for breast cancer patients. These results are in agreement with previous studies (23)(24)(25).…”

Clinicopathological and Prognostic Significance of PRMT5 in Cancers: A System Review and Meta-Analysis

“…Among the left 35 articles, 3 articles could not be used to extract HRs and 95% CIs from the survival curves. Finally, 32 articles were included, 5,8-13,19-43 those articles were published between January 1, 2013 and July 25, 2021. The flow diagram was shown in Figure 1.

Figure 1.Flow diagram of the study selection in the meta-analysis.

…”

Fasting Induces Hepatocellular Carcinoma Cell Apoptosis by Inhibiting SET8 Expression

“…SET8 plays a key role in the epigenetic regulation of genes in many cellular processes [37]. Higher expression of SET8 in tumours is associated with high recurrence and low overall survival [23]. These observations indicate that SET8 may be a potential therapeutic target for tumour therapy.…”

“…Moreover, SET8 is involved in cancer proliferation, invasiveness, and migration and is thus associated with a poor survival rate in cancer patients [21,22]. Some reports show that high methyltransferase activity of SET8 is associated with a high recurrence rate and poor overall survival rate in patients with liver cancer [23]. Consistently, a reduction in SET8 methyltransferase activity increases cellular ROS accumulation [24] and results in massive apoptosis in the epithelium [25].…”