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

Yen-Hao Chen; Chang-Han Chen; Chih-Yen Chien; Yan-Ye Su; Sheng-Dean Luo; Shau-Hsuan Li

doi:10.7717/peerj.13759

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

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

Authors

Yen-Hao Chen^{1

2

3}, Chang-Han Chen^{4

5}, Chih-Yen Chien⁶, Yan-Ye Su⁶, Sheng-Dean Luo⁶, Shau-Hsuan Li¹

Affiliations

¹ Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
² School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³ Department of Nursing, School of Nursing, Fooyin University, Kaohsiung, Taiwan.
⁴ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
⁵ Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
⁶ Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

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.

Keywords: JMJD3; Oral tongue cancer; Squamous cell carcinoma; Surgery.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell* / genetics
Head and Neck Neoplasms*
Humans
Jumonji Domain-Containing Histone Demethylases / genetics
Male
Neoplastic Processes
Squamous Cell Carcinoma of Head and Neck
Tongue Neoplasms* / genetics

Substances

Jumonji Domain-Containing Histone Demethylases

Grants and funding

This work was supported by Chang Gung Memorial Hospital, grant number CMRPG8K0601. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.