College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
Clinical Laboratory, Dalian Municipal Central Hospital, Dalian 116033, China.
Cells. 2022 Aug 8;11(15):2453. doi: 10.3390/cells11152453.
Pancreatic cancer (PC) remains one of the top 10 causes of cancer-related death in recent years. Approximately 80% of PC patients are diagnosed at the middle or advanced stage and miss the opportunity for surgery. The demand for early diagnostic methods and reliable biomarkers is increasing, although a number of tumor markers such as CA19-9 and CEA have already been utilized in clinics. In this study, we analyzed the alteration of -glycan of serum glycoproteins by mass spectrometry and lectin blotting. The results showed that bisecting GlcNAc structures of glycoproteins are significantly increased in PC patients' sera. With (PHA-E) lectin that specifically recognizes bisecting GlcNAc -glycans, the serum glycoproteins bearing bisecting GlcNAc in PC patients' sera were pulled down and identified by nano-LC-MS/MS. Among them, ceruloplasmin (Cp) was screened out with a satisfied sensitivity and specificity in identifying PC from acute pancreatitis patients (AUC: 0.757) and normal healthy persons (AUC: 0.972), suggesting a close association between Cp and PC development and diagnosis. To prove that, the Cp expression in tumor tissues of PC patients was examined. The results showed that Cp was significantly upregulated in PC tissues compared to that in adjacent normal tissues. All these results suggested that PHA-E-positive Cp could be a potential PC-specific glycoprotein marker to distinguish PC patients from acute pancreatitis patients and normal persons.
胰腺癌（PC）仍然是近年来癌症相关死亡的前 10 大原因之一。大约 80%的 PC 患者在中期或晚期被诊断出来，错过了手术的机会。尽管已经有一些肿瘤标志物，如 CA19-9 和 CEA，在临床上得到了应用，但对早期诊断方法和可靠的生物标志物的需求仍在增加。在本研究中，我们通过质谱和凝集素印迹分析了血清糖蛋白中-聚糖的变化。结果表明，PC 患者血清中的糖蛋白双分支 GlcNAc 结构显著增加。用特异性识别双分支 GlcNAc-聚糖的 PHA-E 凝集素，从 PC 患者血清中拉下并通过纳升 LC-MS/MS 鉴定携带双分支 GlcNAc 的血清糖蛋白。其中，铜蓝蛋白（Cp）在鉴别 PC 与急性胰腺炎患者（AUC：0.757）和正常健康人（AUC：0.972）方面具有较高的灵敏度和特异性，被筛选出来，表明 Cp 与 PC 的发生和诊断密切相关。为了证明这一点，我们检查了 PC 患者肿瘤组织中的 Cp 表达。结果表明，Cp 在 PC 组织中的表达明显高于相邻正常组织。所有这些结果表明，PHA-E 阳性 Cp 可能是一种潜在的 PC 特异性糖蛋白标志物，可将 PC 患者与急性胰腺炎患者和正常人区分开来。
