Serum Cathepsin B to Cystatin C Ratio as a Potential Marker for the Diagnosis of Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a cancer of the bile duct epithelial cells. The highest incidence rate of CCAwith a poor prognosis and poor response to chemotherapy is found in Southeast Asian countries, especially innortheastern Thailand and Lao PDR. Cathepsin B is a lysosomal cysteine protease which is regulated by cysteineproteinase inhibitors such as cystatin C. Elevation of cathepsin B levels in biological fluid has been observedin patients with inflammatory diseases and many cancers. We aimed to investigate the serum cathepsin B andcystatin C levels of CCA patients to evaluate the feasibility of using cathepsin B and cystatin C as markers forthe diagnosis of CCA. Fifty-six sera from CCA patients, 17 with benign biliary diseases (BBD) and 13 fromcontrols were collected and the cathepsin B and cystatin C levels were determined. In addition, cathepsin Bexpression was investigated immunohistochemically for 9 matched-pairs of cancerous and adjacent tissues ofCCA patients. Serum cathepsin B, but not cystatin C, was significantly higher in CCA and BBD patient groupscompared to that in the control group. Consistently, all cancerous tissues strongly expressed cathepsin B whileadjacent tissues were negative in 7 out of 9 cases. In contrast, serum cystatin C levels were comparable betweenCCA and control groups, although serum cystatin C levels in the BBD group was higher than that in the controlor CCA groups. When the serum cathepsin B to cystatin C ratio was calculated, that of the CCA group wassignificantly higher than that of the control group, and, although statistically not significant, the ratio of CCAgroup showed a trend to be higher than that of the BBD group. Thus, the cathepsin B to cystatin C ratio mightbe used as an alternative marker for aiding diagnosis of CCA.