title: Prognostic and predictive value of cathepsin X in serum from colorectal cancer patients.
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.
authors.forename: Tjaša
authors.initials: T
authors.lastname: Vižin
authors.forename: Ib Jarle
authors.initials: IJ
authors.lastname: Christensen
authors.forename: Michael
authors.initials: M
authors.lastname: Wilhelmsen
authors.forename: Hans Jørgen
authors.initials: HJ
authors.lastname: Nielsen
authors.affiliation: Chair of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia. janko.kos@ffa.uni-lj.si.
authors.forename: Janko
authors.initials: J
authors.lastname: Kos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood; D002403:Cathepsins / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D002403:Cathepsins
references.citation: Int J Biol Markers. 2008 Jul-Sep;23(3):161-8
references.pmid: 18949742
references.citation: Cell Mol Life Sci. 2009 Mar;66(6):1126-34
references.pmid: 19194656
references.citation: Radiol Oncol. 2012 Sep;46(3):207-12
references.pmid: 23077459
references.citation: Cancer Res. 2006 May 15;66(10):5242-50
references.pmid: 16707449
references.citation: Cell Adh Migr. 2009 Apr-Jun;3(2):164-6
references.pmid: 19262176
references.citation: Scand J Gastroenterol. 2008;43(2):242-8
references.pmid: 18224568
references.citation: Exp Dermatol. 2003 Dec;12(6):761-71
references.pmid: 14714555
references.citation: Clin Cancer Res. 2000 Jul;6(7):2712-7
references.pmid: 10914715
references.citation: Int J Biochem Cell Biol. 2009 Aug-Sep;41(8-9):1685-96
references.pmid: 19433310
references.citation: Eur J Cancer. 2004 Jul;40(10):1610-6
references.pmid: 15196548
references.citation: Prostate. 2004 Jul 1;60(2):109-19
references.pmid: 15162377
references.citation: Cancer Cell. 2004 May;5(5):409-10
references.pmid: 15144947
references.citation: Immunology. 2008 May;124(1):76-88
references.pmid: 18194276
references.citation: Biol Chem. 2001 May;382(5):805-10
references.pmid: 11517934
references.citation: Am J Pathol. 2012 Apr;180(4):1485-94
references.pmid: 22330678
references.citation: Oncol Rep. 1998 Nov-Dec;5(6):1349-61
references.pmid: 9769367
references.citation: PLoS Med. 2012;9(5):e1001216
references.pmid: 22675273
references.citation: Cancer Res. 2002 Dec 1;62(23):6803-7
references.pmid: 12460888
references.citation: Cancer Lett. 2007 Apr 28;249(1):87-96
references.pmid: 17275174
references.citation: Eur J Clin Invest. 2010 Jul;40(7):591-9
references.pmid: 20482593
references.citation: Stat Med. 1996 Feb 28;15(4):361-87
references.pmid: 8668867
references.citation: Eur J Cell Biol. 2011 Aug;90(8):678-86
references.pmid: 21616554
references.citation: Proteomics. 2013 Jul;13(14):2069-71
references.pmid: 23677805
references.citation: J Immunol Methods. 2006 Jan 20;308(1-2):241-50
references.pmid: 16376371
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2497-502
references.pmid: 20133781
references.citation: Scand J Gastroenterol. 2010;45(2):200-7
references.pmid: 20095885
references.citation: Hum Immunol. 2011 May;72(5):426-30
references.pmid: 21354459
references.citation: Biochemistry. 1999 Sep 28;38(39):12648-54
references.pmid: 10504234
references.citation: Arch Biochem Biophys. 2005 Apr 15;436(2):323-32
references.pmid: 15797245
references.citation: J Biol Chem. 2006 Dec 22;281(51):39588-97
references.pmid: 17065156
references.citation: PLoS One. 2013;8(1):e53918
references.pmid: 23326535
references.citation: Radiol Oncol. 2011 Jun;45(2):102-15
references.pmid: 22933943
references.citation: J Pathol. 2005 Sep;207(1):32-42
references.pmid: 16025436
references.citation: PLoS One. 2011;6(9):e24967
references.pmid: 21966391
references.citation: Scand J Gastroenterol. 2011 Jan;46(1):60-9
references.pmid: 20799911
references.citation: Exp Cell Res. 2006 Aug 1;312(13):2515-27
references.pmid: 16774752
references.citation: Zhongguo Fei Ai Za Zhi. 2013 Aug 20;16(8):411-6
references.pmid: 23945244
references.citation: Clin Chem. 2008 Dec;54(12):e11-79
references.pmid: 19042984
references.citation: Pathol Res Pract. 2008;204(7):491-500
references.pmid: 18573619
references.citation: Haematologica. 2010 Sep;95(9):1452-60
references.pmid: 20494937
references.citation: Exp Cell Res. 2005 May 15;306(1):103-13
references.pmid: 15878337