Open Access Highly Accessed Research article

Prognostic and predictive value of cathepsin X in serum from colorectal cancer patients

Tjaša Vižin1, Ib Jarle Christensen23, Michael Wilhelmsen4, Hans Jørgen Nielsen45 and Janko Kos16*

Author Affiliations

1 Chair of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia

2 The Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark

3 Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark

4 Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark

5 Institute of Clinical Medicine, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark

6 Department of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia

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BMC Cancer 2014, 14:259  doi:10.1186/1471-2407-14-259

Published: 13 April 2014

Abstract

Background

Cathepsin X is a cysteine protease involved in mechanisms of malignant progression. It is secreted from tumour cells as a proenzyme and may serve to predict the disease status and risk of death for cancer patients. In a previous, pilot, study on 77 colorectal patients we demonstrated the correlation of higher serum levels with shorter overall survival.

Methods

264 patients with colorectal cancer were included in a prospectively accrued multi-centre observational cohort study with the aim of testing novel biomarkers. Blood samples were collected before preoperative large bowel endoscopy and total cathepsin X was measured in sera by ELISA. As a control group we selected at random 77 subjects who had no findings at endoscopy and reported no co-morbidity.

Results

The mean level of cathepsin X in cancer patients did not differ from the control levels (23.4 ng/ml ± 6.4 SD vs. 18.8 ng/ml ± 11.4 SD, p > 0.05) and there was no association with age, gender, disease stage, tumour location or CEA. In univariate analysis no association between cathepsin X levels and overall survival was demonstrated for the entire set of patients, however, cathepsin X was associated with survival in a group of patients with local resectable disease (stages I-III) (HR = 1.69, 95% CI: 1.03-2.75, p = 0.03). For this group, multivariate Cox regression analysis showed an association (HR = 3.13, 95% CI: 1.37-7.18, p = 0.003) between high cathepsin X levels and shorter overall survival for patients who did not receive chemotherapy, whereas, for patients who received chemotherapy, there was no association between cathepsin X and survival (HR = 0.51, 95% CI: 0.20-1.33, p = 0.88).

Conclusions

Association of cathepsin X levels with overall survival was not confirmed for an entire set of 264 colorectal patients, but for patients in stages I-III with local resectable disease. The significant association of cathepsin X with survival in a group of patients who received no chemotherapy and the absence of this association in the group who received chemotherapy, suggest the possible predictive value for response to chemotherapy. The results have to be confirmed in a further prospective study.

Keywords:
Cathepsin X; Colorectal cancer; Prognosis; Predictive marker; Serum biomarker