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血小板衍生生长因子受体β:一种用于非肌层浸润性膀胱癌复发的新型尿液生物标志物。

Platelet-derived growth factor receptor beta: a novel urinary biomarker for recurrence of non-muscle-invasive bladder cancer.

作者信息

Feng Jiayu, He Weifeng, Song Yajun, Wang Ying, Simpson Richard J, Zhang Xiaorong, Luo Gaoxing, Wu Jun, Huang Chibing

机构信息

Department of Urology, Xinqiao Hospital, The Third Military Medical University, Chongqing, China.

Chongqing Key Laboratory for Disease Proteomics; State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing, China.

出版信息

PLoS One. 2014 May 6;9(5):e96671. doi: 10.1371/journal.pone.0096671. eCollection 2014.

Abstract

Non-muscle-invasive bladder cancer (NMIBC) is one of the most common malignant tumors in the urological system with a high risk of recurrence, and effective non-invasive biomarkers for NMIBC relapse are still needed. The human urinary proteome can reflect the status of the microenvironment of the urinary system and is an ideal source for clinical diagnosis of urinary system diseases. Our previous work used proteomics to identify 1643 high-confidence urinary proteins in the urine from a healthy population. Here, we used bioinformatics to construct a cancer-associated protein-protein interaction (PPI) network comprising 16 high-abundance urinary proteins based on the urinary proteome database. As a result, platelet-derived growth factor receptor beta (PDGFRB) was selected for further validation as a candidate biomarker for NMIBC diagnosis and prognosis. Although the levels of urinary PDGFRB showed no significant difference between patients pre- and post-surgery (n = 185, P>0.05), over 3 years of follow-up, urinary PDGFRB was shown to be significantly higher in relapsed patients (n = 68) than in relapse-free patients (n = 117, P<0.001). The levels of urinary PDGFRB were significantly correlated with the risk of 3-year recurrence of NMIBC, and these levels improved the accuracy of a NMIBC recurrence risk prediction model that included age, tumor size, and tumor number (area under the curve, 0.862; 95% CI, 0.809 to 0.914) compared to PDGFR alone. Therefore, we surmise that urinary PDGFRB could serve as a non-invasive biomarker for predicting NMIBC recurrence.

摘要

非肌层浸润性膀胱癌(NMIBC)是泌尿系统中最常见的恶性肿瘤之一,复发风险高,仍需要有效的NMIBC复发非侵入性生物标志物。人类尿液蛋白质组可以反映泌尿系统微环境的状态,是泌尿系统疾病临床诊断的理想来源。我们之前的工作利用蛋白质组学在健康人群尿液中鉴定出1643种高可信度尿液蛋白。在此,我们基于尿液蛋白质组数据库,利用生物信息学构建了一个由16种高丰度尿液蛋白组成的癌症相关蛋白质-蛋白质相互作用(PPI)网络。结果,选择血小板衍生生长因子受体β(PDGFRB)作为候选生物标志物进行进一步验证,用于NMIBC的诊断和预后评估。虽然术前和术后患者尿液中PDGFRB水平无显著差异(n = 185,P>0.05),但经过3年的随访,复发患者(n = 68)尿液中的PDGFRB显著高于无复发患者(n = 117,P<0.001)。尿液中PDGFRB水平与NMIBC 3年复发风险显著相关,与单独的PDGFR相比,这些水平提高了包含年龄、肿瘤大小和肿瘤数量的NMIBC复发风险预测模型的准确性(曲线下面积,0.862;95%CI,0.809至0.914)。因此,我们推测尿液中的PDGFRB可作为预测NMIBC复发的非侵入性生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8c6/4011858/0ff073692137/pone.0096671.g001.jpg

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