title: The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study.
abstract: BACKGROUND
  The aim of this pilot retrospective study was to investigate the immunohistochemical expression of Cathepsin S (CatS) in three cohorts of colorectal cancer (CRC) patients (n=560).
  
  
  METHODS
  Prevalence and association with histopathological variables were assessed across all cohorts. Association with clinical outcomes was investigated in the Northern Ireland Adjuvant Chemotherapy Trial cohort (n=211), where stage II/III CRC patients were randomised between surgery-alone or surgery with adjuvant fluorouracil/folinic acid (FU/FA) treatment.
  
  
  RESULTS
  Greater than 95% of tumours had detectable CatS expression with significantly increased staining in tumours compared with matched normal colon (P>0.001). Increasing CatS was associated with reduced recurrence-free survival (RFS; P=0.03) among patients treated with surgery alone. Adjuvant FU/FA significantly improved RFS (hazard ratio (HR), 0.33; 95% CI, 0.12-0.89) and overall survival (OS; HR, 0.25; 95% CI, 0.08-0.81) among 36 patients with high CatS. Treatment did not benefit the 66 patients with low CatS, with a RFS HR of 1.34 (95% CI, 0.60-3.19) and OS HR of 1.33 (95% CI, 0.56-3.15). Interaction between CatS and treatment status was significant for RFS (P=0.02) and OS (P=0.04) in a multivariate model adjusted for known prognostic markers.
  
  
  CONCLUSIONS
  These results signify that CatS may be an important prognostic biomarker and predictive of response to adjuvant FU/FA in CRC.
authors: Fusion Antibodies Ltd, Springbank Industrial Estate, Pembroke Loop Rd, Belfast BT17 0QL, Northern Ireland. julie.gormley@fusionantibodies.com
authors: J A
authors: JA
authors: Gormley
authors: S M
authors: SM
authors: Hegarty
authors: A
authors: A
authors: O'Grady
authors: M R
authors: MR
authors: Stevenson
authors: R E
authors: RE
authors: Burden
authors: H L
authors: HL
authors: Barrett
authors: C J
authors: CJ
authors: Scott
authors: J A
authors: JA
authors: Johnston
authors: R H
authors: RH
authors: Wilson
authors: E W
authors: EW
authors: Kay
authors: P G
authors: PG
authors: Johnston
authors: S A
authors: SA
authors: Olwill
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002403:Cathepsins / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D002403:Cathepsins; C028217:cathepsin S; D002955:Leucovorin; D005472:Fluorouracil