Department of Urology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, P.R. China.
AntiCancer Inc, San Diego, CA, U.S.A.
Anticancer Res. 2022 May;42(5):2341-2354. doi: 10.21873/anticanres.15713.
BACKGROUND/AIM: Clear-cell renal cell carcinoma (ccRCC) is a common recalcitrant cancer. However, little is known about biomarkers of ccRCC. In the present study, we investigated the role of guanylate-binding protein 2 (GBP2), an interferon-induced GTPase, in ccRCC and its potential as a biomarker of this disease.
GBP2 expression was analyzed using the Gene Expression Omnibus, The Cancer Genome Atlas, and Human Protein Atlas databases. Univariate and multivariate Cox-regression analyses were used to investigate the prognostic value of GBP2 in ccRCC. In addition, quantitative real-time polymerase chain reactions, western blotting, and immunohistochemistry were performed to confirm the expression of GBP2 in tissues from patients with ccRCC who had undergone radical nephrectomy at the Department of Urology, the First Affiliated Hospital of Chongqing Medical University (Chongqing, P. R. China). Cell-function assays were performed to investigate the effect of GBP2 on Caki-1 human kidney-cancer cells.
Bioinformatics and in vitro experiments showed that the expression of GBP2 was up-regulated in ccRCC tissues and cells and was positively correlated with the malignant clinicopathological parameters of the disease. Univariate and multivariate Cox-regression analyses showed that GBP2 expression was an independent risk factor for the prognosis of ccRCC. Cell-function assays showed that GBP2 expression promoted the proliferation, migration, and invasion of Caki-1 cells through the WNT/β-catenin signaling pathway.
The present results indicate that GBP2 expression may serve as a prognostic biomarker for ccRCC.
背景/目的:透明细胞肾细胞癌(ccRCC)是一种常见的难治性癌症。然而,人们对 ccRCC 的生物标志物知之甚少。在本研究中,我们研究了鸟苷酸结合蛋白 2(GBP2)在 ccRCC 中的作用,GBP2 是一种干扰素诱导的 GTPase,及其作为该疾病生物标志物的潜力。
使用基因表达综合数据库、癌症基因组图谱和人类蛋白质图谱数据库分析 GBP2 的表达。采用单变量和多变量 Cox 回归分析来研究 GBP2 在 ccRCC 中的预后价值。此外,还进行了定量实时聚合酶链反应、蛋白质印迹和免疫组织化学检测,以确认重庆医科大学第一附属医院泌尿外科接受根治性肾切除术的 ccRCC 患者组织中 GBP2 的表达。进行细胞功能测定以研究 GBP2 对 Caki-1 人肾癌细胞的影响。
生物信息学和体外实验表明,GBP2 在 ccRCC 组织和细胞中表达上调,并且与该疾病的恶性临床病理参数呈正相关。单变量和多变量 Cox 回归分析表明,GBP2 表达是 ccRCC 预后的独立危险因素。细胞功能测定表明,GBP2 表达通过 WNT/β-catenin 信号通路促进 Caki-1 细胞的增殖、迁移和侵袭。
本研究结果表明,GBP2 表达可能是 ccRCC 的预后生物标志物。