The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study.
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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DOI：
10.1038/bjc.2011.408
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发表时间：
2011-11-08
影响因子：
8.8
通讯作者：
Olwill, S. A.
中科院分区：
文献类型：
--
作者：
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.
这项试点回顾性研究的目的是调查三组结直肠癌 (CRC) 患者 (n=560) 中组织蛋白酶 S (CatS) 的免疫组织化学表达。在所有队列中评估了患病率及其与组织病理学变量的关联。在北爱尔兰辅助化疗试验队列 (n=211) 中研究了与临床结果的关联，其中 II/III 期 CRC 患者被随机分为单独手术或手术联合氟尿嘧啶/亚叶酸 (FU/FA) 辅助治疗。超过 95% 的肿瘤具有可检测的 CatS 表达，与匹配的正常结肠相比，肿瘤中的染色显着增加 (P>0.001)。在仅接受手术治疗的患者中，CatS 增加与无复发生存率降低相关（RFS；P=0.03）。 FU/FA 辅助治疗显着改善了 36 名高 CatS 患者的 RFS（风险比 (HR)，0.33；95% CI，0.12-0.89）和总生存期（OS；HR，0.25；95% CI，0.08-0.81）。治疗并未使 66 名低 CatS 患者受益，RFS HR 为 1.34（95% CI，0.60-3.19），OS HR 为 1.33（95% CI，0.56-3.15）。在针对已知预后标志物进行调整的多变量模型中，CatS 与治疗状态之间的相互作用对于 RFS (P=0.02) 和 OS (P=0.04) 具有显着意义。这些结果表明，CatS 可能是一种重要的预后生物标志物，可预测 CRC 中辅助 FU/FA 的反应。
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). 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. 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. 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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影响因子：
6
作者：
Flannery, T;Gibson, D;Johnston, PG
通讯作者：
Johnston, PG
影响因子：
158.5
作者：
Kapiteijn, E;Marijnen, CAM;van de Velde, CJH
通讯作者：
van de Velde, CJH
影响因子：
4.3
作者：
Gocheva, Vasilena;Joyce, Johanna A.
通讯作者：
Joyce, Johanna A.
影响因子：
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作者：
Benson, Al B., III
通讯作者：
Benson, Al B., III
影响因子：
4.8
作者：
Koblinski, JE;Dosescu, J;Sloane, BF
通讯作者：
Sloane, BF