组蛋白去乙酰化酶4在人肺腺癌组织中的表达水平及其与化疗耐药的关系

摘要

目的 目前关于组蛋白去乙酰化酶(HDAC)4的表达水平与人肺腺癌化疗耐药的关系研究较少.文中旨在探讨HDAC4在人肺腺癌组织中的表达及其临床意义. 方法 选取南京军区南京总医院肿瘤科及胸外科2006年1月至2007年12月72例多西紫衫醇化疗相对耐药的肺腺癌肿瘤患者的肺腺癌组织标本.按RECIST标准评价近期疗效,分为敏感组(n=32例,包括完全缓解和部分缓解者)和不敏感组(n=40例,包括稳定和进展者).≥HDAC4相对表达最佳临界值(78.7)的组织标本为高表达组(n=35),<78.7的组织标本为低表达组(n=37).实时定量RT-PCR法检测敏感组和不敏感组HDAC4的表达,分析低表达组和高表达组无进展生存分析结果. 结果 不敏感组HDAC4的mRNA表达量明显高于敏感组 [(1.42±0.30) vs (0.60±0.15),P<0.01].HDAC4低表达组患者的中位无进展生存期明显高于高表达组(10.2月 vs 5.8月,P<0.05).结论 在多西紫衫醇化疗相对耐药的肺腺癌肿瘤患者中HDAC4表达的增高,有望成为多西紫衫醇化疗耐药性的预测指标.%Objective There have been few research on the relationship between expression of HDAC4 and chemotherapy resistance in human lung adenocarcinoma.The present study aims to investigate the expression and clinical significance of HDAC4 in human lung adenocarcinoma tissues.Methods We selected 72 tissues in lung adenocarcinoma patients with docetaxel-resistant from January 2006 to December 2007 in Department of Oncology and Thoracic Surgery, Nanjing General Hospital of Nanjing Military Region, then evaluated the recent efficacy according to the RECIST criteria and divided the tissues into "sensitive"(n=32, included complete remission and partial remission) and "insensitive"(n=40, included stability and progress) groups.The expression of HDAC4 in tissues≥the HDAC4 optimal relative expression cut-off value(78.7) was high level HDAC4 group(n=35), otherwise it was low level HDAC4 group(n=37).QRT-PCR analysis was performed to detect the HDAC4 expression levels in sensitive group and insensitive group.Analyzed the progression free survival in high level HDAC4 group and low level HDAC4 group.Results The expression of HDAC4 was significantly higher in the insensitive group compared with the sensitive group [(1.42±0.30) vs (0.60±0.15), P<0.01].The median progression free survival was significantly shortened in the high level HDAC4 group compared with the low level HDAC4 group (10.2 months vs 5.8 months, P<0.05).ConclusionThe expression of HDAC4 increased in docetaxel-resistant lung adenocarcinoma patients, and it is expected to be a predictive indicator of the resistance of docetaxel.