The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study |
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Authors: | Gormley J A Hegarty S M O'Grady A Stevenson M R Burden R E Barrett H L Scott C J Johnston J A Wilson R H Kay E W Johnston P G Olwill S A |
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Institution: | Fusion Antibodies Ltd, Springbank Industrial Estate, Pembroke Loop Rd, Belfast BT17 0QL, Northern Ireland. julie.gormley@fusionantibodies.com |
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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.Conclusion: These results signify that CatS may be an important prognostic biomarker and predictive of response to adjuvant FU/FA in CRC. |
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Keywords: | Cathepsin S colorectal cancer predictive prognostic recurrence-free survival |
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