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三种泌尿生殖系统癌症中尿糖蛋白的比较及前列腺癌特异性糖蛋白的鉴定

Comparing Urinary Glycoproteins among Three Urogenital Cancers and Identifying Prostate Cancer-Specific Glycoproteins.

作者信息

Chen Shao-Yung, Lih Tung-Shing Mamie, Li Qing Kay, Zhang Hui

机构信息

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore 21287-0010, Maryland, United States.

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore 21218-2625, Maryland, United States.

出版信息

ACS Omega. 2022 Mar 8;7(11):9172-9180. doi: 10.1021/acsomega.1c05223. eCollection 2022 Mar 22.

Abstract

Prostate cancer, bladder cancer, and renal cancers are major urogenital cancers. Of which, prostate cancer is the most commonly diagnosed and second leading cause of cancer death for men in the United States. For urogenital cancers, urine is considered as proximate body fluid to the tumor site for developing non-invasiveness tests. However, the specific molecular signatures from different urogenital cancers are needed to relate changes in urine to various cancer detections. Herein, we utilized a previously published C4-Tip and C18/MAX-Tip workflow for enrichment of glycopeptides from urine samples and evaluated urinary glycopeptides for its cancer specificity. We analyzed 66 urine samples from bladder cancer ( = 27), prostate cancer ( = 4), clear cell renal cell carcinoma (ccRCC, = 3), and benign plastic hyperplasia (BPH, = 32) and then compared them with a previous publication that reported glycopeptides associated with aggressive prostate cancer (Gleason score ≥ 8). We further demonstrated the cancer specificity of the glycopeptides associated with aggressive prostate cancer. In this study, a total of 33 glycopeptides were identified to be specifically differentially expressed in prostate cancer compared to other urogenital cancer types as well as BPH urines. By cross-comparison with our previous urinary glycoproteomic dataset for aggressive prostate cancer, we reported a total of four glycopeptides from glycoproteins DSC2, MGAM, PIK3IP1, and CD55, commonly identified to be prostate cancer-specific. Together, these results deepen our understanding of the urinary glycoproteins associated with urogenital cancer types and expand our knowledge of the cancer specificity of urinary glycoproteins among urogenital cancer progression.

摘要

前列腺癌、膀胱癌和肾癌是主要的泌尿生殖系统癌症。其中,前列腺癌是美国男性中最常被诊断出的癌症,也是癌症死亡的第二大原因。对于泌尿生殖系统癌症,尿液被认为是最接近肿瘤部位的体液,可用于开发非侵入性检测。然而,需要不同泌尿生殖系统癌症的特定分子特征来将尿液中的变化与各种癌症检测联系起来。在此,我们利用先前发表的C4-Tip和C18/MAX-Tip工作流程从尿液样本中富集糖肽,并评估尿糖肽的癌症特异性。我们分析了来自膀胱癌(n = 27)、前列腺癌(n = 4)、透明细胞肾细胞癌(ccRCC,n = 3)和良性前列腺增生(BPH,n = 32)的66份尿液样本,然后将它们与之前一篇报道与侵袭性前列腺癌(Gleason评分≥8)相关糖肽的文献进行比较。我们进一步证明了与侵袭性前列腺癌相关糖肽的癌症特异性。在这项研究中,共鉴定出33种糖肽在前列腺癌中与其他泌尿生殖系统癌症类型以及BPH尿液相比有特异性差异表达。通过与我们之前关于侵袭性前列腺癌的尿糖蛋白质组数据集进行交叉比较,我们报告了来自糖蛋白DSC2、MGAM、PIK3IP1和CD55的总共四种糖肽,它们通常被鉴定为前列腺癌特异性。总之,这些结果加深了我们对与泌尿生殖系统癌症类型相关的尿糖蛋白 的理解,并扩展了我们对泌尿生殖系统癌症进展过程中尿糖蛋白癌症特异性的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2d3/8945184/cc3054ca581a/ao1c05223_0002.jpg

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