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

TY - JOUR

T1 - Prognostic and predictive value of cathepsin X in serum from colorectal cancer patients

AU - Vižin, Tjaša

AU - Christensen, Ib Jarle

AU - Wilhelmsen, Michael

AU - Nielsen, Hans Jørgen

AU - Kos, Janko

PY - 2014/4/13

Y1 - 2014/4/13

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Carcinoembryonic Antigen

KW - Cathepsins

KW - Colorectal Neoplasms

KW - Disease-Free Survival

KW - Female

KW - Humans

KW - Lymphatic Metastasis

KW - Male

KW - Middle Aged

KW - Neoplasm Staging

KW - Prognosis

KW - Proportional Hazards Models

KW - Tumor Markers, Biological

U2 - 10.1186/1471-2407-14-259

DO - 10.1186/1471-2407-14-259

M3 - Journal article

C2 - 24725597

SN - 1471-2407

VL - 14

SP - 1

EP - 8

JO - B M C Cancer

JF - B M C Cancer

M1 - 259

ER -