Plasma hydroxyproline, MMP‐7 and collagen I as novel predictive risk markers of hepatobiliary disease‐associated cholangiocarcinoma

Abstract

Chronic opisthorchiasis caused by Opisthorchis viverrini infection is characterized by advanced periductal fibrosis leading to hepatobiliary diseases (HBD), including cholangiocarcinoma (CCA). We aimed to determine fibrotic markers to differentiate HBD status including opisthorchiasis, benign biliary disease (BBD) and CCA. Candidate fibrotic markers in plasma of healthy individuals (n = 14) and patients with opisthorchiasis (n = 32, pre‐ and post‐treatment with praziquantel), BBD (n = 31), CCA (n = 37) and other types of tumors (n = 14) were measured by ELISA and zymography. Plasma levels of hydroxyproline (HYP), collagen I, MMP‐7 and TIMP2 in opisthorchiasis patients were significantly higher than those in healthy individuals, and MMP9/TIMP2 balance may be associated with tissue resorption after praziquantel treatment. HYP and TIMP‐2 levels were significantly correlated with periductal fibrosis status evaluated by ultrasonography. Plasma HYP level of CCA patients was the highest among HBD patients (p < 0.05). ROC curves revealed HYP, MMP‐7 and collagen I levels significantly distinguished opisthorchiasis, BBD and CCA (p < 0.001). Odd ratio (OR) analysis demonstrated these markers in opisthorchiasis were predictable for BBD risk (p < 0.05; OR = 28.50, 10.12 and 4.63 for collagen I, MMP‐7 and HYP, respectively), and the risk was reduced by praziquantel treatment. Interestingly, only plasma HYP level in BBD was predictable for CCA risk (OR = 3.69; p = 0.020). In conclusion, plasma HYP, collagen I and MMP‐7 may be useful as novel predictive markers of opisthorchiasis‐related BBD, and HYP may be used as a diagnostic marker for CCA.

Diagnostic and prognostic serum marker of cholangiocarcinoma (Review)

“…The sensitivity and specificity of serum MMP-7 is 53–76.32% and 46.88–92%, respectively, but at different cut-off values, this varies ( Table I ). ROC curve analysis revealed that the detection of the serum MMP-7 level is a reasonably accurate method for the differentiation of CCA from benign biliary tract disease patients [area under curve (AUC), 0.73–0.84] ( 23 , 34 , 35 ).…”

Rotavirus Reassortant–Induced Murine Model of Liver Fibrosis Parallels Human Biliary Atresia

“…The increased presence of MMP‐7 in human serum has been implicated in the pathogenesis of acute and chronic inflammatory conditions of the liver . Thus, we measured the serum levels of MMP‐7 in three group of mice.…”

“…The increased presence of MMP-7 in human serum has been implicated in the pathogenesis of acute and chronic inflammatory conditions of the liver. (28,29) Thus, we measured the serum levels of MMP-7 in three group of mice. At 2 weeks postinoculation higher levels of MMP-7 (P < 0.0005) were detected in serum of T R(VP2,VP4)inoculated mice than saline-inoculated controls (Fig.…”

Risk biomarkers for assessment and chemoprevention of liver fluke-associated cholangiocarcinoma

“…Subsequently, we applied these fibrotic markers to humans for screening of different degrees of fibrosis grading in HBD including CCA. We found that plasma hydroxyproline, MMP7 and collagen I could be used as a fibrotic marker to discriminate HBD‐associated CCA . Moreover, high level of antibody in the plasma against purified Ov antigen associated with HBD and CCA, which might be used as potential marker of HBD and CCA .…”