秦嘉沛, 卢迪, 李涛, 翟今朝, 白怡冰, 王安, 周鑫, 马志强, 胡毅. 组蛋白去乙酰化酶11在肺鳞癌中的表达及预后意义[J]. 解放军医学院学报. DOI: 10.12435/j.issn.2095-5227.2024.096
引用本文: 秦嘉沛, 卢迪, 李涛, 翟今朝, 白怡冰, 王安, 周鑫, 马志强, 胡毅. 组蛋白去乙酰化酶11在肺鳞癌中的表达及预后意义[J]. 解放军医学院学报. DOI: 10.12435/j.issn.2095-5227.2024.096
QIN Jiapei, LU Di, LI Tao, ZHAI Jinzhao, BAI Yi-bing, WANG An, ZHOU Xin, MA Zhiqiang, HU Yi. Expression of histone deacetylase (HDAC) 11 in lung squamous cell carcinoma and its prognostic significance[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL. DOI: 10.12435/j.issn.2095-5227.2024.096
Citation: QIN Jiapei, LU Di, LI Tao, ZHAI Jinzhao, BAI Yi-bing, WANG An, ZHOU Xin, MA Zhiqiang, HU Yi. Expression of histone deacetylase (HDAC) 11 in lung squamous cell carcinoma and its prognostic significance[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL. DOI: 10.12435/j.issn.2095-5227.2024.096

组蛋白去乙酰化酶11在肺鳞癌中的表达及预后意义

Expression of histone deacetylase (HDAC) 11 in lung squamous cell carcinoma and its prognostic significance

  • 摘要:
    背景 肺鳞状细胞癌(Lung squamous cell carcinoma,LUSC)是非小细胞肺癌的主要亚型。既往研究已经揭示了肺鳞状细胞癌中多种基因和通路的改变。然而,针对肺鳞状细胞癌的靶向治疗迄今尚未成功,且治疗方案有限。因此,寻找新的靶点以改善肺鳞状细胞癌患者的生存预后至关重要。
    目的 探究组蛋白去乙酰化酶11(Histone deacetylase 11,HDAC11)在肿瘤组织中的表达与LUSC患者临床病理特征的关系及其对预后的影响。
    方法 选取2009年5月至2014年1月期间在第四军医大学唐都医院确诊的LUSC患者,收集LUSC组织及邻近正常组织样本,使用免疫组织化学染色法统计分析组织中HDAC11表达。随访患者生存情况,绘制Kaplan-Meier生存曲线分析HDAC11表达与LUSC患者总生存期(Overall survival,OS)及无进展生存(Disease-free survival,DFS)的关系。使用GEPIA 2数据库“生存分析”模块绘制K-M生存曲线进一步验证HDAC11基因与LUSC患者生存和预后之间的联系。
    结果 共纳入77例LUSC患者病例,病理组织分析发现HDAC11在LUSC组织中的表达高于癌旁组织,差异有统计学意义(P<0.05)。随访截至2022年11月1日,50例患者死亡。Cox回归分析显示HDAC11高表达是患者不良预后的独立关联因素(HR:2.275,95% CI:1.256 ~ 4.120;P=0.007),高表达HDAC11的LUSC患者死亡风险更高(HR:1.54,95% CI:2.5 ~ 3.5;P=0.034)。来源于GEPIA 2数据库LUSC病例的生存分析也证实了HDAC11表达与患者的OS(HR:1.5,P=0.0037)和DFS(HR:1.7,P=0.027)关联。此外,在GEPIA 2数据库中我们识别了与HDAC11表达相似的基因,这些基因涉及细胞迁移、运输等生理过程,并与STAT3、MDM2等癌基因存在显著关联,提示HDAC11可能通过调控这些基因影响肿瘤发生。
    结论 HDAC11的高表达与LUSC患者的不良预后有关,有望成为LUSC患者全新的治疗靶点和疗效评判标准。

     

    Abstract:
    Background Lung squamous cell carcinoma (LUSC) is a major subtype of non-small cell Lung cancer. Previous studies have revealed various genetic and pathway alterations in lung squamous cell carcinoma. However, targeted therapy for LUSC has not yet been successful so far, and the treatment options are limited. Therefore, it is crucial to identify new targets to improve the survival prognosis of patients with LUSC.
    Objective To explore the relationship between the expression of Histone deacetylase 11(HDAC11) in tumor tissues and the clinicopathological characteristics of LUSC patients and its effect on prognosis.
    Methods Selection of LUSC patients diagnosed at Tangdu Hospital of the Fourth Military Medical University from May 2009 to January 2014, collection of LUSC tissue and adjacent normal tissue samples, and immunohistochemical staining was used to statistically analyze the expression of HDAC11 in these tissues. The survival status of the patients was followed up, and Kaplan-Meier survival curves were constructed to analyze the relationship between HDAC11 expression and the overall survival (OS) as well as disease-free survival (DFS) of LUSC patients. Furthermore, the "Survival Analysis" module of the GEPIA 2 database was utilized to draw K-M survival curves, aiming to further validate the association between HDAC11 gene and the survival and prognosis of LUSC patients.
    Results A total of 77 LUSC patients were enrolled. Pathological tissue analysis found that the expression of HDAC11 in LUSC tissues was higher than that in adjacent non-cancer tissues, and the difference was statistically significant (P<0.05). The follow-up ended on November 1, 2022, and 50 patients died. Cox regression analysis showed that high HDAC11 expression was an independent risk factor for poor prognosis (HR: 2.275, 95% CI: 1.256-4.120; P=0.007), with high expression of HDAC11 LUSC higher risk of death (HR: 1.54, 95% CI: 2.5-3.5; P=0.034). Survival analysis of LUSC cases from the GEPIA 2 database also confirmed that HDAC11 expression was associated with OS (HR:1.5, P=0.0037) and DFS (HR:1.7, P=0.027). In addition, we identified genes with similar expression to HDAC11 in the GEPIA 2 database, which were involved in physiological processes such as cell migration and transport, and were significantly associated with oncogenes such as STAT3 and MDM2, suggesting that HDAC11 may affect tumorigenesis by regulating these genes.
    Conclusion High expression of HDAC11 related to LUSC patients with poor prognosis is expected to become LUSC patients new therapeutic targets and curative effect evaluation standard.

     

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