Jia Wei, Chang Bin, Sun Lili, Zhu Huimin, Pang Lijuan, Tao Lin, Zou Hong, Du Jinze, Dong Yuling, Qi Yan, Jiang Jinfang, Liang Weihua, Li Feng, Zhao Xia
Department of Pathology, Shihezi University School of Medicine Shihezi, China.
Department of Pathology, Shanghai Cancer Hospital of Fudan University Shanghai, China.
Int J Clin Exp Pathol. 2014 Aug 15;7(9):5940-9. eCollection 2014.
We investigated the clinical significance of regulated in development and DNA damage response (REDD1) and p-AKT expression in human ovarian cancer (OC), explored the correlation of KRAS mutations with REDD1 expression, and assessed the therapeutic relevance of REDD1 in OC. We collected and immunohistochemically analyzed 118 formalin-fixed paraffin-embedded tumor tissue samples (100 primary OC and 18 borderline tumors) and 14 normal fallopian tubes, for REDD1 and p-AKT expression. Direct DNA sequencing for KRAS mutations and quantitative real-time polymerase chain reaction for detecting REDD1 mRNA expression were performed. REDD1 and p-AKT expressions were significantly higher in serous adenocarcinoma than other histological types, and this increase positively correlated with late-stage disease. REDD1 expression correlated with ascites formation, while p-AKT expression correlated with higher histological grade and chemoresistance. Kaplan Meier survival analysis showed significantly reduced disease-free survival (DFS) and overall survival (OS) in OC patients with both REDD1 and p-AKT overexpression. Patients with KRAS mutations had a longer DFS and OS. However, KRAS mutation and REDD1 over-expression was not correlated. Together, REDD1 and p-AKT over-expression may serve as a prognostic biomarker in OC, but KRAS mutations and REDD1 protein over-expression were not correlated in OC. We believe that with increasing knowledge of the role of REDD1 in cell migration, invasion, and proliferation pathways, the potential of REDD1 as a therapeutic target in OC may be uncovered.
我们研究了发育调控与DNA损伤反应（REDD1）及p-AKT表达在人卵巢癌（OC）中的临床意义，探讨了KRAS突变与REDD1表达的相关性，并评估了REDD1在OC中的治疗相关性。我们收集了118份福尔马林固定石蜡包埋的肿瘤组织样本（100例原发性OC和18例交界性肿瘤）以及14份正常输卵管组织样本，采用免疫组织化学方法分析REDD1和p-AKT的表达情况。进行了KRAS突变的直接DNA测序以及检测REDD1 mRNA表达的定量实时聚合酶链反应。浆液性腺癌中REDD1和p-AKT的表达显著高于其他组织学类型，且这种增加与疾病晚期呈正相关。REDD1表达与腹水形成相关，而p-AKT表达与更高的组织学分级和化疗耐药性相关。Kaplan Meier生存分析显示，REDD1和p-AKT均过表达的OC患者的无病生存期（DFS）和总生存期（OS）显著缩短。KRAS突变的患者DFS和OS更长。然而，KRAS突变与REDD1过表达无相关性。总之，REDD1和p-AKT过表达可能作为OC的预后生物标志物，但OC中KRAS突变与REDD1蛋白过表达无相关性。我们相信，随着对REDD1在细胞迁移、侵袭和增殖途径中作用的认识不断增加，REDD1作为OC治疗靶点的潜力可能会被发现。
