组蛋白去乙酰化酶11在肺鳞癌中的表达及预后意义OACSTPCD
Expression of histone deacetylase(HDAC)11 in lung squamous cell carcinoma and its prognostic significance
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—2014年1月在空军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分析组织中HDAC11表达.随访患者的生存情况,分析HDAC11表达与LUSC患者总生存期(overall survival,OS)关系.使用GEPIA 2数据库中LUSC资料进一步验证HDAC11基因与生存及预后的联系,并对相关基因和蛋白进行分析.结果 共纳入 77例LUSC患者,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,中位OS为 2.4年.高表达HDAC11的LUSC患者中位生存期更短[1.9(95%CI:1.7~3.3)年vs 3.2(95%CI:2.7~4.0)年],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).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OS(HR=1.709,95%CI:1.525~1.956)关联.此外,在GEPIA 2数据库中本课题组识别了与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患者的不良预后相关,有望成为LUSC患者全新的治疗靶点和疗效评判标准.
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 LUSC patients diagnosed at Tangdu Hospital of the Fourth Military Medical University from May 2009 to January 2014 were selected,and LUSC tissue and adjacent normal tissue samples were collected.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)of LUSC patients.Furthermore,the data of LUSH cases in the GEPIA 2 database was utilized to further validate the association between HDAC11 gene and the survival and prognosis of LUSC patients,and related genes and proteins were also analyzed.Results A total of 77 LUSC patients were enrolled.Pathological results showed 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).As of November 1,2022,50 patients had died,with an overall survival(OS)of 2.4 years for the patient cohort.LUSC patients with high expression of HDAC11 had poor median survival(1.9[95%CI:1.7-3.3]yrs vs 3.2[95%CI:2.7-4.0]yrs).Cox regression analysis showed that high HDAC11 expression was independently associated with risk of poor prognosis(HR=2.275,95%CI:1.256-4.120,P=0.007).Survival analysis of LUSC cases from the GEPIA 2 database also confirmed that HDAC11 expression was associated with OS(HR=1.709,95%CI:1.525-1.956).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,which suggested that HDAC11 might affect tumorigenesis by regulating these genes.Conclusion The high expression of HDAC11 is associated with the poor prognosis in LUSC patients,which is expected to become a new therapeutic target and efficacy evaluation standard for LUSC patients.
秦嘉沛;卢迪;李涛;翟今朝;白怡冰;王安;周鑫;马志强;胡毅
解放军医学院,北京 100853||解放军总医院第五医学中心肿瘤医学部,全军肿瘤学重点实验室,肿瘤靶向治疗和抗体药物教育部重点实验室,北京 100039解放军总医院第五医学中心肿瘤医学部,全军肿瘤学重点实验室,肿瘤靶向治疗和抗体药物教育部重点实验室,北京 100039||解放军空军军医大学唐都医院胸外科,陕西西安 710038解放军总医院第五医学中心肿瘤医学部,全军肿瘤学重点实验室,肿瘤靶向治疗和抗体药物教育部重点实验室,北京 100039
临床医学
组蛋白去乙酰化酶11肺鳞癌免疫组化预后
histone deacetylase 11lung squamous cell carcinomaimmunocytochemistryprognosis
《解放军医学院学报》 2024 (008)
824-831 / 8
国家卫健委专项重点课题(GWJJ2021100304)
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