Ohyama Chikara, Yoneyama Tohru, Tobisawa Yuki, Ishikawa Tomokazu, Hatakeyama Shingo, Koie Takuya, Mori Kazuyuki
Rinsho Byori. 2017 Feb;65(2):210-217.
Prostate cancer (PCa) is now the most common male malignant tumor in both Japan and Western countries. Prostate-specific antigen (PSA) has been widely used for the early detection of PCa; however, it is not an ideal biomarker due to its low specificity. Aberrant glycosylation is closely associated with malignant transformation and cancer progression. Recent advances in glycobiology techniques can be applied to the development of novel biomarkers for PCa. We previously identified PCa-associated aberrant glycosylation on PSA, that is, α2,3-linked sialylation as an additional terminal N-glycan on free PSA(S2,3PSA). We then developed a new assay system for the measurement of S2,3PSA utilizing the μTAS method. The area under the curve (AUC) for the detection of PCa with the %S2,3PSA ratio was significantly better than that with total PSA. Another urgent issue in clinical practice for PCa is the over-treatment of patients with a low malignant potential, as aggressive treatment is not necessary. To overcome this problem, it is essential to develop a useful tool for the measurement of the malignant potential. Core2 ,β-1,6-N-acetylglucosaminyltransferase-1 (GCNT1, C2GnT) is a key enzyme that forms core 2-branched 0-glycans. Its expression is associated with the progression of several cancers. We established a mouse IgG monoclonal antibody (mAb) against GCNT1 and examined the relationship of GCNT1 expression with the clinicopathological status of PCa. GCNT1- negative patients were associated with significantly better PSA-free survival compared with GCNT1-positive patients. Furthermore, we established new methods for GCNT1 detection using urine samples of PCa patients. Immunoblotting was used to examine post-digital rectal examination (DRE) urine from PCa patients. Over 90% of GCNT1-positive PCa patients with high concentrations of serum PSA showed extracapsular extension in prostatectomy specimens. In conclusion, the clinical application of glycobiology techniques is a promising approach to develop novel biomarkers for PCa.
前列腺癌（PCa）如今是日本和西方国家最常见的男性恶性肿瘤。前列腺特异性抗原（PSA）已被广泛用于PCa的早期检测；然而，由于其低特异性，它并非理想的生物标志物。异常糖基化与恶性转化和癌症进展密切相关。糖生物学技术的最新进展可应用于开发PCa的新型生物标志物。我们之前在PSA上鉴定出与PCa相关的异常糖基化，即α2,3-连接的唾液酸化作为游离PSA（S2,3PSA）上额外的末端N-聚糖。然后我们开发了一种利用微流控芯片技术（μTAS）测量S2,3PSA的新检测系统。用%S2,3PSA比值检测PCa的曲线下面积（AUC）显著优于总PSA。PCa临床实践中的另一个紧迫问题是对恶性潜能低的患者过度治疗，因为没必要进行积极治疗。为克服这一问题，开发一种测量恶性潜能的有用工具至关重要。核心2 β-1,6-N-乙酰葡糖胺基转移酶-1（GCNT1，C2GnT）是形成核心2分支O-聚糖的关键酶。其表达与多种癌症的进展相关。我们制备了一种针对GCNT1的小鼠IgG单克隆抗体（mAb），并研究了GCNT1表达与PCa临床病理状态的关系。与GCNT1阳性患者相比，GCNT1阴性患者的无PSA生存期显著更好。此外，我们利用PCa患者的尿液样本建立了检测GCNT1的新方法。免疫印迹法用于检测PCa患者直肠指检（DRE）后的尿液。血清PSA浓度高的GCNT1阳性PCa患者中，超过90%在前列腺切除标本中显示有包膜外侵犯。总之，糖生物学技术的临床应用是开发PCa新型生物标志物的一种有前景的方法。
