Serum cathepsin H as a potential prognostic marker in patients with colorectal cancer

Abstract

Cathepsin H is a lysosomal cysteine protease that may participate in tumor progression. In order to evaluate its potential as a prognostic marker, its protein levels were measured by ELISA in preoperative sera from 324 patients with colorectal cancer. The level of cathepsin H was significantly increased in patient sera, the median level was 8.4 ng/mL versus 2.1 ng/mL in 90 healthy blood donors (p < 0.0001). A weak association of cathepsin H levels was found with patient age (p = 0.02) but not with Dukes' stage, sex, or the level of carcinoembryonic antigen (CEA). In survival analysis a significant difference was found between the group of patients with low cathepsin H (first tertile) who had a poor prognosis and the remaining patients (p = 0.03). The risk of patients was further stratified when cathepsin H levels were combined with CEA. Patients with high CEA and low cathepsin H had the highest risk of death with a hazard ratio of 2.72 (95% CI 1.73-4.28), p < 0.0001. Our results show that the prognostic information of cathepsin H differs from that of the related cathepsins B and L and suggest different roles during the progression of malignant disease.

Cathepsin B, Cathepsin H, Cathepsin X and Cystatin C in Sera of Patients with Early-Stage and Inflammatory Breast Cancer

“…*Serum levels are expressed as median (interquartile range) † P value for comparison of premenopausal versus postmenopausal, and negative versus positive subgroups **Data from noninflammatory invasive breast cancers only is significantly higher than the levels we previously measured in healthy controls (23,30). Like for cathepsin B, the levels of cathepsin H in sera of patients with earlystage breast cancer (lymph node negative) also exceeded the reported levels for control sera (23,28,29). This is consistent with the data reported for other cancer types and with the study of Gabrijelcic and coworkers reporting highly elevated levels of cathepsin H in sera of breast cancer patients (6).…”

“…In the last decade, numerous studies have detected cathepsin B and H expression in sera from patients with various cancer types, suggesting that these markers may provide diagnostic information (23)(24)(25)(26)(27)(28)(29). So far, the relative increase in cathepsin H serum levels with respect to controls was larger than for cathepsin B in patients with melanoma, colorectal cancer and lung cancer (23,28,29). In the present study, the median serum cathepsin B level of all 207 breast cancer patients was 16.0 ng/mL.…”

Relationship between Drug Release of DE-310, Macromolecular Prodrug of DX-8951f, and Cathepsins Activity in Several Tumors

“…12) On the other hand, cathepsin H is highly expressed in colon cancer cells, 13) and cathepsin L is secreted in metastatic bone marrow tumor.…”

“…10) Cathepsin B is expressed more highly in malignant tumors 11) and is responsible for destruction of basal membranes, processing of matrix proteases, and inactivation of protein inhibitors. 12) On the other hand, cathepsin H is highly expressed in colon cancer cells, 13) and cathepsin L is secreted in metastatic bone marrow tumor.…”

“…Expression of cathepsins B, H, and L in tumor tissues and their involvement in tumor progression have been indicated. 10) Cathepsin B is expressed more highly in malignant tumors 11) and is responsible for destruction of basal membranes, processing of matrix proteases, and inactivation of protein inhibitors.12) On the other hand, cathepsin H is highly expressed in colon cancer cells, 13) and cathepsin L is secreted in metastatic bone marrow tumor.14) It is likely that the level of cathepsin species in tumor tissues would be one of the factors determining antitumor activity of DE-310.In this study, we examined the drug release from DE-310 by cathepsins B, H, and L obtained from human liver to identify the products of hydrolysis and determine the rate of hydrolysis for each cathepsin species. Then, we examined in vitro drug release from DE-310 in different murine or human tumor cell types, in addition to the activity or expression of cathepsins B, H and L in the cells.…”