Canary Center at Stanford for Cancer Early Detection, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.
Department of Urology, Stanford University School of Medicine, Stanford, CA, 94305, USA.
Sci Rep. 2018 Apr 25;8(1):6509. doi: 10.1038/s41598-018-24270-w.
Currently prostate-specific antigen is used for prostate cancer (PCa) screening, however it lacks the necessary specificity for differentiating PCa from other diseases of the prostate such as benign prostatic hyperplasia (BPH), presenting a clinical need to distinguish these cases at the molecular level. Protein glycosylation plays an important role in a number of cellular processes involved in neoplastic progression and is aberrant in PCa. In this study, we systematically interrogate the alterations in the circulating levels of hundreds of serum proteins and their glycoforms in PCa and BPH samples using multi-lectin affinity chromatography and quantitative mass spectrometry-based proteomics. Specific lectins (AAL, PHA-L and PHA-E) were used to target and chromatographically separate core-fucosylated and highly-branched protein glycoforms for analysis, as differential expression of these glycan types have been previously associated with PCa. Global levels of CD5L, CFP, C8A, BST1, and C7 were significantly increased in the PCa samples. Notable glycoform-specific alterations between BPH and PCa were identified among proteins CD163, C4A, and ATRN in the PHA-L/E fraction and among C4BPB and AZGP1 glycoforms in the AAL fraction. Despite these modest differences, substantial similarities in glycoproteomic profiles were observed between PCa and BPH sera.
目前，前列腺特异性抗原（PSA）被用于前列腺癌（PCa）的筛查，但它缺乏将 PCa 与前列腺的其他疾病（如良性前列腺增生（BPH））区分开来的必要特异性，因此需要在分子水平上区分这些病例。蛋白质糖基化在涉及肿瘤进展的许多细胞过程中起着重要作用，并且在 PCa 中异常。在这项研究中，我们使用多凝集素亲和层析和基于定量质谱的蛋白质组学方法，系统地研究了 PCa 和 BPH 样本中数百种血清蛋白及其糖型的循环水平变化。使用特定的凝集素（AAL、PHA-L 和 PHA-E）来靶向和色谱分离核心岩藻糖基化和高度分支的蛋白质糖型进行分析，因为这些糖型的差异表达先前与 PCa 相关。在 PCa 样本中，CD5L、CFP、C8A、BST1 和 C7 的水平显著升高。在 PHA-L/E 部分中，CD163、C4A 和 ATRN 蛋白以及在 AAL 部分中 C4BPB 和 AZGP1 糖型之间，鉴定出了 BPH 和 PCa 之间显著的糖型特异性差异。尽管存在这些微小差异，但在 PCa 和 BPH 血清的糖蛋白组学图谱中观察到了相当大的相似性。
