Phaseolus vulgaris Erythroagglutinin (PHA-E)-Positive Ceruloplasmin Acts as a Potential Biomarker in Pancreatic Cancer Diagnosis

Abstract

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 N-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 Phaseolus vulgaris Erythroagglutinin (PHA-E) lectin that specifically recognizes bisecting GlcNAc N-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.