Association between histone deacetylase 9 (HDAC9) level and poor prognosis of lung squamous cell cancer patients
- VernacularTitle:组蛋白去乙酰化酶 9 表达水平与肺鳞癌不良预后相关性研究
- Author:
Jiwang BI
1
;
Bing LIU
1
;
Yuanyuan MA
1
;
Yue YANG
1
Author Information
1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery Ⅱ, Peking University Cancer Hospital and Institute for Cancer Research, Beijing, 100142, P.R.China
- Publication Type:Journal Article
- Keywords:
Histone deacetylase;
non-small cell lung cancer;
squamous cell carcinoma;
immunohistochemistry;
CRISPR-Cas system
- From:
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery
2020;27(06):649-656
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the expression level of histone deacetylase 9 (HDAC9) in lung squamous cell carcinoma (LUSC) tissues, to analyze its correlations with clinicopathological characteristics and prognosis of LUSC patients, and to explore the effect it exerts on the proliferation of LUSC cells. Methods The expression level of HDAC9 was detected by immunohistochemistry staining (IHC), and its correlations with clinicopathological characteristics were analyzed by χ2 test. Survival analysis was performed using Kaplan-Meier method. Univariate and multivariate Cox proportional hazards model were employed to analyze independent predictors for overall survival (OS) of LUSC patients. CRISPR/dCas9 activation system was used to activate the transcription of HDAC9 gene in LUSC cell line EBC-1. CCK8 cell proliferation assay and colony formation test were performed to investigate the effect that transcriptional activation of HDAC9 exerts on the proliferation of LUSC cells. Results Of the 129 LUSC patients, 39 (30.2%) were in the HDAC9 low expression group and 90 (69.8%) were in the HDAC9 high expression group. The OS of the patients with HDAC9 high expression was shorter than that of patients with HDAC9 low expression (P=0.032). The expression level of HDAC9 was associated with tumor grade (P=0.035), primary tumor size (P=0.041), and lymph node metastasis (P=0.013). The expression level of HDAC9 (P=0.023), tumor grade (P=0.003), primary tumor size (P=0.003), and lymph node metastasis (P=0.002) were independent predictors for OS of LUSC patients. Transcriptional activation of HDAC9 promoted colony formation of LUSC cells and cell proliferating curves showed that LUSC cells with HDAC9 transcriptional activation proliferated faster than non-targeting cells (F=52.7, P=0.002). Conclusion LUSC patients with HDAC9 high expression have poorer prognosis than HDAC9 low expression ones. The expression level of HDAC9 is associated with tumor grade, primary tumor size, and lymph node metastasis, and is identified as an independent predictor for prognosis of LUSC. Transcriptional activation of HDAC9 promotes cell proliferation in LUSC. These results suggest that HDAC9 may serve as a promising biomarker for prognosis in LUSC.
