J Cancer 2020; 11(11):3256-3263. doi:10.7150/jca.36801 This issue

Research Paper

High level of H3K4 tri-methylation modification predicts poor prognosis in esophageal cancer

Xu-Dong Ye1, Bai-Quan Qiu1*, Dian Xiong1,2*, Xu Pei1*, Na Jie3, Hua Xu1, Shu-Qiang Zhu1, Xiang Long1, Zheng Xu1, Hai-Bo Wu1, Jian-Jun Xu1, You-Sheng Huang3✉, Yong-Bing Wu1✉

1. Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Jiangxi Province 330000, P. R. China.
2. Department of Thoracic Surgery, The Central Hospital of Xuhui District, Shanghai, 20031, P. R. China
3. Department of Pathology, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan 571101, P.R. China
*These authors have an equal contribution in this work; No previous presentation or publication of material in any way appears in this article.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Ye XD, Qiu BQ, Xiong D, Pei X, Jie N, Xu H, Zhu SQ, Long X, Xu Z, Wu HB, Xu JJ, Huang YS, Wu YB. High level of H3K4 tri-methylation modification predicts poor prognosis in esophageal cancer. J Cancer 2020; 11(11):3256-3263. doi:10.7150/jca.36801. Available from https://www.jcancer.org/v11p3256.htm

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Objectives: An increase in the trimethylation of lysine 4 of histone 3 (H3K4me3) has been reported to be involved in the development of several types of tumors. However, the level and role of H3K4me3 in human esophageal cancer (HEC) remain unknown. Here, we assessed the role and clinical significance of H3K4me3 in HEC.

Methods: The level of H3K4me3 was determined in 15 pairs of HEC and paracancerous tissues by Western blotting. A tissue microarray including samples from 100 HEC patients was analyzed by immunohistochemistry to determine the relationship between the level of H3K4me3 and the clinicopathological features of HEC patients. Then, the levels of H3K4me3 in HEC cells were elevated via knockdown of inhibitor of growth family member 4(Ing4) expression. Finally, the prognostic significance of H3K4me3 levels in HEC patients was further analyzed.

Results: We found that H3K4me3 levels were frequently elevated in HEC tissues compared with adjacent esophageal tissues, and elevated H3K4me3 was significantly associated with poor tumor differentiation (p =1.39×10-5) and advanced tumor stage (p=8.5×10-5). After Ing4 knockdown in HEC cells, we found that the cell proliferation, metastasis, invasion and colony formation abilities were enhanced compared to those in the control cells. Notably, we found that HEC patients with a high level of H3K4me3 exhibited an unfavorable 5-year survival rate compared to those with a low level of H3K4me3 (p=6.8×10-5). The univariate analysis showed that the tumor differentiation, TNM stage, and H3K4me3 level were predictors of the overall survival rate of HEC patients. In the multivariate analysis, tumor stage (p=0.015) and H3K4me3 level (p=0.034) were revealed to be independent parameters for predicting the prognosis of HEC patients.

Conclusions: Thus, high levels of H3K4me3 may be used as a meaningful biomarker for HEC prognosis evaluation.

Keywords: H3K4me3, HEC, prognosis