Zheng Linfeng, Zhu Yuping, Lei Lei, Sun Wenyong, Cheng Guoping, Yang Shifeng
Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
Department of Colorectal Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
Oncol Lett. 2018 Jan;15(1):568-574. doi: 10.3892/ol.2017.7344. Epub 2017 Nov 3.
Checkpoint kinase 1 (CHK1) and p53 are involved in cell-cycle checkpoint, and cellular response to DNA damage. CHK1 and p53 are overexpressed in bladder urothelial carcinoma (BUC); however, a clear elucidation on their interaction and influence in the progress of BUC is absent. The aim of the present study was to examine the correlation between CHK1 and p53 in BUC, and analyze their value as therapeutic targets and prognostic indicators in BUC. A clinically annotated cohort of 110 patients with BUC was identified retrospectively. EnVision-based immunohistochemistry and western blot analysis of the aforementioned DNA repair proteins were conducted on formalin-fixed-paraffin-embedded or frozen tissues from the primary tumor. A total of 45 peritumoral tissue cases were assessed similarly as the control group. In the cohort of 110 patients with BUC, a significant overexpression of CHK1 and p53 was observed in primary compared with the peritumoral tissues (P<0.05). CHK1 and p53 demonstrated a positive correlation in BUC, and both were positively associated with the histological grade, clinical pathological staging, lymphatic metastasis and the 5-year survival rate (P<0.05). However, CHK1 and p53 were not associated with sex, age, tumor diameter, single/multiple sites or incipient/recurrence. The overexpression of CHK1 and p53, and their synergistic interaction were putatively correlated with the physiology of BUC that may be deemed as potential therapeutic targets and prognostic indicators.
检查点激酶1(CHK1)和p53参与细胞周期检查点以及细胞对DNA损伤的反应。CHK1和p53在膀胱尿路上皮癌(BUC)中过表达;然而,关于它们在BUC进展中的相互作用和影响尚无明确阐述。本研究的目的是检测BUC中CHK1和p53之间的相关性,并分析它们作为BUC治疗靶点和预后指标的价值。回顾性确定了一个有临床注释的110例BUC患者队列。对来自原发性肿瘤的福尔马林固定石蜡包埋或冷冻组织进行基于EnVision的免疫组织化学和上述DNA修复蛋白的蛋白质印迹分析。总共45例瘤周组织病例作为对照组进行类似评估。在110例BUC患者队列中,与瘤周组织相比,原发性肿瘤中CHK1和p53明显过表达(P<0.05)。CHK1和p53在BUC中呈正相关,且均与组织学分级、临床病理分期、淋巴转移和5年生存率呈正相关(P<0.05)。然而,CHK1和p53与性别、年龄、肿瘤直径、单/多发部位或初发/复发无关。CHK1和p53的过表达及其协同相互作用可能与BUC的生理状态相关,可被视为潜在的治疗靶点和预后指标。