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JMJD3 抑制接受手术切除的口腔舌鳞状细胞癌患者的肿瘤进展。

JMJD3 suppresses tumor progression in oral tongue squamous cell carcinoma patients receiving surgical resection.

机构信息

Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

出版信息

PeerJ. 2022 Jul 13;10:e13759. doi: 10.7717/peerj.13759. eCollection 2022.

Abstract

BACKGROUND

Jumonji domain-containing-3 (JMJD3) is reported to be a histone H3 lysine 27 (H3K27) demethylase and a tumor suppressor gene. The present study designed to investigate the crucial role of JMJD3 in oral tongue squamous cell carcinoma (OTSCC) patients who received surgical resection.

METHODS

We enrolled a total of 156 OTSCC patients receiving surgical resection, including 73 patients (47%) with high expression of JMJD3 and 83 patients (53%) harboring low expression of JMJD3. Two OTSCC cell lines, SAS and Cal 27, were used to explore the modulation of cancer. GSK-J4, a potent inhibitor of JMJD3, was used to treat the two OTSCC cell lines. The Chi-square test was performed to examine between-group differences in categorical variables; the Kaplan-Meier method was used to investigate survival outcome in univariate analysis, and the Cox regression model was used for multivariate analysis.

RESULTS

The median follow-up period was 59.2 months and he five-year disease-free survival (DFS) and overall survival (OS) rates were 46.2% and 50.0%, respectively. Better five-year DFS (59% versus 35%) and five-year OS (63% versus 39%) were mentioned in patients with high expression of JMJD3 compared to those with low expression of JMJD3. High expression of JMJD3 was significantly associated with superior DFS and OS in the univariate and multivariate analyses. Following successful inhibition of JMJD3 by GSK-J4, western blotting analysis showed the decreased expression of Rb and p21.

CONCLUSION

Our study showed that high expression of JMJD3 is a good prognostic factor in OTSCC patients who underwent surgical resection.

摘要

背景

含 JMJD3 结构域蛋白(JMJD3)被报道为组蛋白 H3 赖氨酸 27(H3K27)去甲基化酶和抑癌基因。本研究旨在探讨 JMJD3 在接受手术切除的口腔舌鳞状细胞癌(OTSCC)患者中的关键作用。

方法

我们共纳入 156 例接受手术切除的 OTSCC 患者,其中 73 例(47%)JMJD3 高表达,83 例(53%)JMJD3 低表达。使用两种 OTSCC 细胞系 SAS 和 Cal 27 来探讨癌症的调控。使用强效的 JMJD3 抑制剂 GSK-J4 处理这两种 OTSCC 细胞系。使用卡方检验比较分类变量组间的差异;Kaplan-Meier 法用于单因素分析中的生存结果,Cox 回归模型用于多因素分析。

结果

中位随访时间为 59.2 个月,五年无病生存率(DFS)和总生存率(OS)分别为 46.2%和 50.0%。JMJD3 高表达的患者的五年 DFS(59%对 35%)和五年 OS(63%对 39%)均优于 JMJD3 低表达的患者。JMJD3 高表达在单因素和多因素分析中均与较好的 DFS 和 OS 显著相关。GSK-J4 成功抑制 JMJD3 后,western blot 分析显示 Rb 和 p21 的表达降低。

结论

我们的研究表明,在接受手术切除的 OTSCC 患者中,JMJD3 高表达是一个良好的预后因素。

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