A combination of serum leucine-rich α-2-glycoprotein 1, CA19-9 and interleukin-6 differentiate biliary tract cancer from benign biliary strictures

Abstract

Background:Biliary tract cancer (BTC) and benign biliary strictures can be difficult to differentiate using standard tumour markers such as serum carbohydrate antigen 19-9 (CA19-9) as they lack diagnostic accuracy.Methods:Two-dimensional difference gel electrophoresis and tandem mass spectrometry were used to profile immunodepleted serum samples collected from cases of BTC, primary sclerosing cholangitis (PSC), immunoglobulin G4-associated cholangitis and healthy volunteers. The serum levels of one candidate protein, leucine-rich α-2-glycoprotein (LRG1), were verified in individual samples using enzyme-linked immunosorbent assay and compared with serum levels of CA19-9, bilirubin, interleukin-6 (IL-6) and other inflammatory markers.Results:We report increased LRG1, CA19-9 and IL-6 levels in serum from patients with BTC compared with benign disease and healthy controls. Immunohistochemical analysis also demonstrated increased staining of LRG1 in BTC compared with cholangiocytes in benign biliary disease. The combination of receiver operating characteristic (ROC) curves for LRG1, CA19-9 and IL-6 demonstrated an area under the ROC curve of 0.98. In addition, raised LRG1 and CA19-9 were found to be independent predictors of BTC in the presence of elevated bilirubin, C-reactive protein and alkaline phosphatase.Conclusion:These results suggest LRG1, CA19-9 and IL-6 as useful markers for the diagnosis of BTC, particularly in high-risk patients with PSC.

Serum leucine-rich α2-glycoprotein is a useful biomarker for monitoring disease activity in patients with adult-onset Still’s disease

“…These results suggest the possibility of LRG as a marker for the differential diagnosis between AOSD and RA in patients presenting with polyarthritis. However, elevated serum LRG levels have been reported in patients with bacterial infection, malignancies and inflammatory bowel diseases (4,14,15). These results collectively suggest that LRG may not be a specific diagnostic marker but is a useful marker to monitor inflammatory burden in AOSD.…”

Screening differential expression of serum proteins in AFP-negative HBV-related hepatocellular carcinoma using iTRAQ –MALDI-MS/MS

“…One study suggested a potential use in the diagnosis of bladder cancer, as increased levels were reported in the urine [30]. In another study, high levels were found in biliary tract cancer compared with cholangiocytes in benign biliary disease [31].…”

Genetic alteration regulated by microRNAs in biliary tract cancers

“…In addition, owing to lack of specific clinical symptoms, CC and GBC, characterized by notorious difficulty in diagnosis, high mortality as well as poor sensitivity to conventional therapies, always advance terminal stage with serious invasion and metastasis to other organs [80,81]. It is also difficult to distinguish BTCs and benign biliary diseases by detecting the standard tumor markers such as serum carbohydrate antigen 19-9 (CA19-9) with low diagnostic accuracy [82]. Pathological diagnosis on the biopsy obtained either via endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) is still considered as gold standard for BTC diagnosis to certify whether the neoplasm is malignancy [83].…”