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p53β:在中位随访 5.3 年时,用于预测透明细胞肾细胞癌患者预后的一个新的标志物。

p53β: a new prognostic marker for patients with clear-cell renal cell carcinoma from 5.3 years of median follow-up.

机构信息

Minimally Invasive Urology Center, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.

School of Basic Medical Sciences, Shandong University, Jinan, China.

出版信息

Carcinogenesis. 2018 Mar 8;39(3):368-374. doi: 10.1093/carcin/bgy001.

Abstract

We previously reported six different p53 isoforms in renal cell carcinoma (RCC). In the present study, influences of p53β on recurrence-free survival (RFS) and overall survival (OS) were evaluated. Patients diagnosed with RCC in our center were into this study. mRNA expressions of p53 isoforms (p53α, p53β, p53γ) in tumors were determined by RT-PCR and real-time PCR. Functional yeast-based assay was performed to analyze p53 mutational status. p53β transfected 786-O and CAKi-1 cells were cultured to examine expressions of B-cell lymphoma 2-associated X protein (bax) and caspase-3, and ratios of apoptosis. After surgeries, all patients were followed up at programmed intervals. 266 patients were analyzed in this study. Median follow-up time was 5.3 years. RT-PCR (r = -0.72, P = 0.016) and real-time PCR (r = -0.65, P = 0.033) both showed only p53β expressed higher level in lower tumor stage versus higher stage. p53 wild-type and p53 mutation had comparable RFS (P = 0.361) and OS (P = 0.218), respectively. Kaplan-Meier analysis showed high p53β expression was associated with significantly improved RFS and OS, regardless of p53 mutational status. High p53β expression indicated better RFS [hazard ratio (HR) 2.599, 95% confidence interval (CI) 1.472-4.551, P = 0.038] and OS (HR 2.604, 95% CI 1.453-4.824, P = 0.031). p53β transfected 786-O and CAKi-1 cells expressed significantly higher level of bax and caspase-3, and had higher ratios of apoptosis than untransfected cells. Taken together, higher level of p53β predict better prognosis in patients with RCC through enhancing apoptosis in tumors.

摘要

我们之前曾报道过肾癌(RCC)中存在六种不同的 p53 异构体。在本研究中,评估了 p53β 对无复发生存(RFS)和总生存(OS)的影响。将在我们中心诊断为 RCC 的患者纳入本研究。通过 RT-PCR 和实时 PCR 测定肿瘤中 p53 异构体(p53α、p53β、p53γ)的 mRNA 表达。进行了基于酵母的功能测定以分析 p53 突变状态。培养 p53β 转染的 786-O 和 CAKi-1 细胞以检测 B 细胞淋巴瘤 2 相关 X 蛋白(bax)和半胱天冬酶-3 的表达以及凋亡的比例。手术后,所有患者均按计划间隔进行随访。本研究共分析了 266 例患者。中位随访时间为 5.3 年。RT-PCR(r = -0.72,P = 0.016)和实时 PCR(r = -0.65,P = 0.033)均显示仅在肿瘤分期较低时 p53β 的表达水平较高。p53 野生型和 p53 突变型的 RFS(P = 0.361)和 OS(P = 0.218)相当。Kaplan-Meier 分析显示,无论 p53 突变状态如何,高 p53β 表达均与 RFS 和 OS 显著改善相关。高 p53β 表达表明 RFS 更好[风险比(HR)2.599,95%置信区间(CI)1.472-4.551,P = 0.038]和 OS(HR 2.604,95% CI 1.453-4.824,P = 0.031)。p53β 转染的 786-O 和 CAKi-1 细胞表达的 bax 和半胱天冬酶-3 明显更高,凋亡比例更高。总之,p53β 水平升高可通过增强肿瘤细胞凋亡来预测 RCC 患者的预后更好。

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