Serum levels of the N-terminal fragment of connective tissue growth factor is a novel biomarker for chronic pancreatitis

Abstract

Chronic inflammation of the pancreas is considered to be one of the causes of pancreatic cancer. However, the diagnosis of chronic pancreatitis (CP) is very difficult in the pancreas, where biopsies are difficult to perform. The prevalence of CP is estimated to be many times more common than in patients with actual symptomatic CP. In recent years, abnormal cleavage of certain proteins has attracted attention as a biomarker for CP other than pancreatic enzymes. Connective tissue growth factor (CTGF) is one of the growth factors involved in tissue repair and other processes and is increased by stimulation of transforming growth factor-β, suggesting a relationship of CTGF with fibrosis. In this study, we measured the total length of CTGF in blood and N-terminal fragment CTGF in 48 cases of chronic pancreatitis, 64 cases of pancreatic cancer and 45 healthy volunteers (HV). Interestingly, we found that blood N-terminal fragment CTGF level was significantly increased in CP and pancreatic cancer patients. Multiple logistic regression analysis showed serum levels of N-terminal fragment CTGF, CRP and amylase were significant and independent variables for the differential diagnosis of CP from HV. Receiver operating characteristic analysis showed that area under the curve (AUC) value of serum N-terminal fragment CTGF level was 0.933, which can differentiate between CP and HV. Several factors would be involved in the increase in serum N-terminal fragment CTGF level. In conclusion, serum N-terminal fragment CTGF level is a promising new biomarker for CP.

Fig. 1

Serum levels of CTGF in 48 patients with chronic pancreatitis and 45 healthy volunteers Serum levels of total CTGF (A), full-length CTGF (B), and N-terminal fragments of CTGF (C) were determined using each ELISA. Each dot on the graph represents one individual. Box plot shows maximum, third quartile, median, first quartile, and minimum values.

Fig. 2

ROC analyses evaluating CTGF as a biomarker for chronic pancreatitis Panel A presents the ROC curve for levels of full-length CTGF for discrimination of CP patients from HV subjects. Panel B presents the ROC curve for levels of N-terminal fragments of CTGF for discrimination of CP patients from HV subjects. Panel C presents the ROC curve for the ratio of the N-terminal CTGF fragment/full-length CTGF levels for discrimination of CP patients from HV subjects. AUC: area under the curve, Sen: sensitivity, Spe: specificity, PPV: positive predictive value, NPV: negative predictive value.