The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study

被引：62

作者：

Gormley, J. A. ^{[1
]}

Hegarty, S. M. ^{[2
]}

O'Grady, A. ^{[3
]}

Stevenson, M. R. ^{[4
]}

Burden, R. E. ^{[1
,5
]}

Barrett, H. L. ^{[3
]}

Scott, C. J. ^{[5
]}

Johnston, J. A. ^{[1
,6
]}

Wilson, R. H. ^{[7
]}

Kay, E. W. ^{[3
]}

Johnston, P. G. ^{[7
]}

Olwill, S. A. ^{[1
]}

机构：

[1] Fus Antibodies Ltd, Belfast BT17 0QL, Antrim, North Ireland

[2] Queens Univ Belfast, Ctr Med Educ, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland

[3] Beaumont Hosp, Dept Histopathol, Royal Coll Surg Ireland, Dublin 9, Ireland

[4] Queens Univ Belfast, Ctr Publ Hlth, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland

[5] Queens Univ Belfast, Sch Pharm, Belfast, Antrim, North Ireland

[6] Queens Univ Belfast, Ctr Infect & Immun, Belfast, Antrim, North Ireland

[7] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Sch Med Dent & Biomed Sci, Belfast, Antrim, North Ireland

来源：

BRITISH JOURNAL OF CANCER | 2011年 / 105卷 / 10期

关键词：

Cathepsin S; colorectal cancer; predictive; prognostic; recurrence-free survival; COLORECTAL-CANCER; MICROSATELLITE-INSTABILITY; CYSTEINE CATHEPSINS; TUMOR PROGRESSION; COLON-CANCER; STAGE-II; EXPRESSION; BREAST; METASTASIS; INHIBITION;

D O I：

10.1038/bjc.2011.408

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. British Journal of Cancer (2011) 105, 1487-1494. doi:10.1038/bjc.2011.408 www.bjcancer.com Published online 11 October 2011 (C) 2011 Cancer Research UK

引用

页码：1487 / 1494

页数：8

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