Serum Mac-2 binding protein is a novel biomarker for chronic pancreatitis

AIM: To determine the efficacy of Mac-2 binding protein (Mac-2bp) for diagnosis of chronic pancreatitis.METHODS: Fifty-nine healthy volunteers (HV), 162 patients with chronic pancreatitis (CP), and 94 patients with pancreatic ductal adenocarcinoma (PDAC) were enrolled in this study. We measured serum Mac-2bp using our developed enzyme-linked immunosorbent assay kit. Additional biochemical variables were measured using an automated analyzer (including aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, triglyceride, C-reactive protein, and amylase levels) or chemiluminescent enzyme immunoassay (carbohydrate antigen 19-9 and carcinoembryonic antigen). The ability of Mac-2bp to predict CP diagnosis accurately was assessed using receiver operating characteristic (ROC) analyses.RESULTS: Serum Mac-2bp levels were significantly increased in CP patients compared to HV (P < 0.0001) and PDAC patients (P < 0.0001). Area under the ROC curve values of Mac-2bp for the discrimination of CP from HV and PDAC were 0.727 and 0.784, respectively. Multivariate analyses demonstrated that serum Mac-2bp levels were independent determinants for CP diagnosis from HV and PDAC patients. Immunohistological staining showed that Mac-2bp was expressed faintly in the pancreas tissues of both CP and PDAC patients. Serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, and triglyceride levels were significantly higher in patients with CP or PDAC. Serum Mac-2bp levels were highly correlated with protein levels of alanine aminotransferase, γ-glutamyltransferase, and C-reactive protein, but not amylase, suggesting that the damaged liver produces Mac-2bp.CONCLUSION: Measurement of serum Mac-2bp may be a novel and useful biomarker for CP diagnosis as well as liver fibrosis in the general population.

Fucosylation is a common glycosylation type in pancreatic cancer stem cell-like phenotypes

AIM: To evaluate/isolate cancer stem cells(CSCs) from tissue or cell lines according to various definitions and cell surface markers. METHODS: Lectin microarray analysis was conducted on CSC-like fractions of the human pancreatic cancer cell line Panc1 by establishing anti-cancer drug-resistant cells. Changes in glycan structure of CSC-like cells were also investigated in sphere-forming cells as well as in CSC fractions obtained from overexpression of CD24 and CD44. RESULTS: Several types of fucosylation were increased under these conditions, and the expression of fucosylation regulatory genes such as fucosyltransferases, GDP-fucose synthetic enzymes, and GDP-fucose transporters were dramatically enhanced in CSC-like cells. These changes were significant in gemcitabineresistant cells and sphere cells of a human pancreatic cancer cell line, Panc1. However, downregulation of cellular fucosylation by knockdown of the GDP-fucose transporter did not alter gemcitabine resistance, indicating that increased cellular fucosylation is a result of CSC-like transformation. CONCLUSION: Fucosylation might be a biomarker of CSC-like cells in pancreatic cancer.

Detection of fucosylated haptoglobin using the 10-7G antibody as a biomarker for evaluating endoscopic remission in ulcerative colitis

BACKGROUND Inflammatory bowel disease(IBD)is a chronic,relapsing inflammation of the digestive tract.Although fecal and serum biomarkers have been extremely important and supportive for monitoring of IBD,their low sensitivity and high variability characteristics limit clinical efficacy.Thus,the establishment of better biomarkers is expected.Fucosylation is one of the most important glycosylation modifications of proteins.Fucosylated haptoglobin(Fuc-Hpt)is used as a biomarker for several cancers and inflammation-related diseases.We recently established a novel glycan monoclonal antibody(mAb),designated 10-7G,which recognizes Fuc-Hpt.We developed an enzyme-linked immunosorbent assay(ELISA)to measure serum levels of Fuc-Hpt(10-7G values).AIM To investigate the usefulness of the serum 10-7G values as a potential biomarker for monitoring disease activity in IBD.METHODS This was a case control study.Intestinal tissues of IBD patients(n=10)were examined immunohistochemically using the 10-7G mAb.We determined 10-7G values using serum from patients with ulcerative colitis(UC,n=110),Crohn’s disease(n=45),acute enteritis(AE,n=11),and healthy volunteers(HVs)who exhibited normal(n=20)or high(n=79)C-reactive protein(CRP)levels at medical check-up.We investigated the correlation between the 10-7G value and various clinical parameters of IBD patients by correlation analysis.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the usefulness of the 10-7G values as a biomarker for clinical and endoscopic remission of UC compared to conventional serum biomarkers.RESULTS In the immunohistochemical analysis,positive 10-7G mAb staining was observed in lymphocytes infiltrating into inflammatory sites of the mucosal layer and lymphoid follicles.The 10-7G values were significantly higher in patients with IBD(P<0.001)and AE(P<0.05)compared with HVs.In addition,10-7G values were correlated with clinical examination parameters related to inflammation in patients with UC,particularly the CRP level(rs=0.525,P=0.003)and clinical activity index score(rs=0.435,P=0.038).However,there was no correlation between 10-7G values and CRP in HVs with high CRP levels,suggesting that the 10-7G values is not the same as a general inflammation biomarker.ROC curve analysis showed that area under the curve(AUC)value of 10-7G values for the diagnosis of endoscopic remission was higher than other biomarkers(AUC value=0.699).CONCLUSION The serum 10-7G value is a novel biomarker for evaluating intestinal inflammation and endoscopic mucosal healing in UC.