直肠癌中HuR表达水平及其对新辅助放化疗所致DNA损伤效应的影响  

Expression of HuR in middle-low rectal cancer and its efficacy in neoadjuvant chemoradiation therapy response

作　　者：方昌义 杨明威[2] 李韵松[1] 杨阳[1] 何佳慧 余昌俊[1] Fang Changyi;Yang Mingwei;Li Yunsong(Dept of General Surgery,The First Affiliated Hospital of Anhui Medical University,Hefei 230022;Radiotherapy,The First Affiliated Hospital of Anhui Medical University,Hefei 230022)

机构地区：[1]安徽医科大学第一附属医院普外科,合肥230022 [2]安徽医科大学第一附属医院放疗科,合肥230022 [3]安徽医科大学第一附属医院病理科,合肥230022

出　　处：《安徽医科大学学报》2021年第4期613-618,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然青年科学基金(编号:81902451)。

摘　　要：目的探讨RNA结合蛋白人类抗原R(HuR)在直肠癌组织中的表达水平及其对新辅助放化疗所致DNA损伤效应的影响。方法收集并检测56例中低位(定义为经硬质结/直肠镜测量肿瘤下缘距肛缘≤12 cm)直肠腺癌组织标本对中的HuR表达水平,并分析HuR相对表达水平与患者术后临床病理参数之间的联系。采集并运用免疫组化检测33例初始评估无法根治性切除且行新辅助放化疗的中低位直肠癌患者的肠镜活检石蜡包埋组织标本中的HuR蛋白表达水平,分析其相对表达水平是否影响中低位直肠癌新辅助放化疗的临床客观缓解率。同时在细胞水平(直肠癌细胞株DLD-1)检测HuR水平对电离辐射及化学药物5-氟尿嘧啶(5-FU)所致DNA损伤效应的影响。结果中低位直肠癌组织中HuR蛋白阳性表达率增高,且HuR阳性表达的中低位直肠癌患者的新辅助放化疗临床客观缓解率差于HuR低表达者,差异有统计学意义(P<0.05)。细胞水平彗星实验(Comet assay)显示在直肠癌细胞中敲减HuR表达水平,可增加电离辐射及化疗药物引起的DNA双链断裂(DSBs)的累积。结论HuR高表达的中低位直肠癌患者的新辅助放化疗临床客观缓解率较低,可能与DNA损伤效应机制有关,HuR高表达是导致直肠癌患者放化疗抵抗的关键因素。Objective To explore the expression and its efficacy in predicting neoadjuvant chemoradiation therapy sensitivityof human antigen R(HuR)in rectal cancer.Methods Fifty-six paired middle-low rectal cancer samples and clinicopathologic characteristics were analyzed.HuR expression in middle-low rectal cancer tissuesand exploratory biopsies was detected by quantitative real-time PCR and immunochemistry.The capability of HuR to influence DNA DSBs inthe presence of chemo-radiation was determined by using comet assay.Results HuR was mostly upregulated in middle-low rectal cancer tissues and over expression HuR was significantly associated with invasive clinicopathologic characteristics such as advanced TNM stage,positive lymph node invasion and vascular infiltration.The Kaplan-Meier plot of overall survival from TCGA database demonstrated that high HuR expression patient subgroup had a shorter median survival period compared with the low HuR expression subgroup.Moreover,patients with high HuR expression were of inferior therapeutic sensitivity to chemo-radiation therapy.Conclusion HuR is over expressed in rectal cancer and possessed the capabilities to resist chemo-radiation therapy.In addition,inhibition of HuR can improve chemo-radiationtherapeutic response.

关 键 词：人类抗原R(HuR) 直肠癌 DNA损伤 放化疗抵抗 

分 类 号：R735.34[医药卫生—肿瘤]