School of Biotechnology, Dublin City University, D09 V209 Dublin 9, Ireland.
National Centre for Sensor Research, Biomedical Diagnostics Institute, Dublin City University, D09 V209 Dublin 9, Ireland.
Int J Mol Sci. 2020 Dec 3;21(23):9233. doi: 10.3390/ijms21239233.
The diagnosis and treatment of prostate cancer (PCa) is a major health-care concern worldwide. This cancer can manifest itself in many distinct forms and the transition from clinically indolent PCa to the more invasive aggressive form remains poorly understood. It is now universally accepted that glycan expression patterns change with the cellular modifications that accompany the onset of tumorigenesis. The aim of this study was to investigate if differential glycosylation patterns could distinguish between indolent, significant, and aggressive PCa. Whole serum -glycan profiling was carried out on 117 prostate cancer patients' serum using our automated, high-throughput analysis platform for glycan-profiling which utilizes ultra-performance liquid chromatography (UPLC) to obtain high resolution separation of -linked glycans released from the serum glycoproteins. We observed increases in hybrid, oligomannose, and biantennary digalactosylated monosialylated glycans (M5A1G1S1, M8, and A2G2S1), bisecting glycans (A2B, A2(6)BG1) and monoantennary glycans (A1), and decreases in triantennary trigalactosylated trisialylated glycans with and without core fucose (A3G3S3 and FA3G3S3) with PCa progression from indolent through significant and aggressive disease. These changes give us an insight into the disease pathogenesis and identify potential biomarkers for monitoring the PCa progression, however these need further confirmation studies.
前列腺癌（PCa）的诊断和治疗是全球医疗保健的一个主要关注点。这种癌症可以表现出许多不同的形式，从临床惰性 PCa 向更具侵袭性的侵袭性形式的转变仍未被很好地理解。现在人们普遍认为，糖链表达模式随着伴随肿瘤发生的细胞修饰而改变。本研究旨在探讨差异糖基化模式是否可以区分惰性、显著和侵袭性 PCa。使用我们的自动化高通量聚糖分析平台对 117 名前列腺癌患者的血清进行全血清聚糖谱分析，该平台利用超高效液相色谱（UPLC）对从血清糖蛋白释放的α-连接聚糖进行高分辨率分离。我们观察到，随着前列腺癌从惰性到显著再到侵袭性的进展，杂合型、寡甘露糖型和双触角二半乳糖基化单唾液酸化聚糖（M5A1G1S1、M8 和 A2G2S1）、双触角型（A2B、A2(6)BG1）和单触角型聚糖（A1）增加，而带有和不带有核心岩藻糖的三触角三半乳糖基化三唾液酸化聚糖（A3G3S3 和 FA3G3S3）减少。这些变化使我们深入了解疾病的发病机制，并确定了用于监测前列腺癌进展的潜在生物标志物，但这些仍需要进一步的确认研究。
