Discovery of PTN as a serum-based biomarker of pro-metastatic prostate cancer.

Discovery of PTN as a serum-based biomarker of pro-metastatic prostate cancer.
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发现PTN作为促转移性前列腺癌的基于血清的生物标志物。

DOI:
10.1038/s41416-020-01200-0
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发表时间:
2021-03
影响因子:
8.8
通讯作者:
Stoyanova T
Stoyanova T
中科院分区:
医学1区
文献类型:
--
作者:
Liu S;Shen M;Hsu EC;Zhang CA;Garcia-Marques F;Nolley R;Koul K;Rice MA;Aslan M;Pitteri SJ;Massie C;George A;Brooks JD;Gnanapragasam VJ;Stoyanova T

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区分临床上显著的惰性前列腺癌(PC)是一个主要的临床挑战。我们利用靶向蛋白质生物标志物发现方法来鉴定促转移PC特异性的生物标志物。使用Olink蛋白质组学组分析来自无癌组、剑桥预后组1(CPG 1,低风险)、CPG 5(高风险)和转移性疾病的血清样品。在根治性直肠癌切除术队列(n = 234)中通过免疫组织化学进行组织验证。我们发现,与其他组相比,转移性PC患者中有9种蛋白质(多效生长因子(PTN)、MK、PVRL 4、EPHA 2、TFPI-2、hK 11、SYND 1、ANGPT 2和hK 14)升高。与良性和CPG 1相比,CPG 5男性血清中PTN水平升高。高组织PTN水平是低度和中度疾病生化复发和转移进展的独立预测因素。这些发现表明,PTN可能代表了一种新的生物标志物,存在预后不良的局部疾病,有可能转移,需要进一步研究。
Distinguishing clinically significant from indolent prostate cancer (PC) is a major clinical challenge. We utilised targeted protein biomarker discovery approach to identify biomarkers specific for pro-metastatic PC. Serum samples from the cancer-free group; Cambridge Prognostic Group 1 (CPG1, low risk); CPG5 (high risk) and metastatic disease were analysed using Olink Proteomics panels. Tissue validation was performed by immunohistochemistry in a radical prostatectomy cohort (n = 234). We discovered that nine proteins (pleiotrophin (PTN), MK, PVRL4, EPHA2, TFPI-2, hK11, SYND1, ANGPT2, and hK14) were elevated in metastatic PC patients when compared to other groups. PTN levels were increased in serum from men with CPG5 compared to benign and CPG1. High tissue PTN level was an independent predictor of biochemical recurrence and metastatic progression in low- and intermediate-grade disease. These findings suggest that PTN may represent a novel biomarker for the presence of poor prognosis local disease with the potential to metastasise warranting further investigation.
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