Amplification of SKI Is a Prognostic Marker in Early Colorectal Cancer

Neoplasia: An International Journal for Oncology Research

Richard Herrmann¹  Christoph F. Rochlitz¹  Martin Buess¹  Luigi Terracciano²  Jürgen Reuter³  Jean-Louis Boulay³  Urban Laffer⁴  Urs Metzger⁵  Pierluigi Ballabeni⁶ 

[1] Department of Oncology, University Hospital of Basel, Basel CH-4031, Switzerland;Department of Pathology, University Hospital of Basel, Basel CH-4031, Switzerland;Department of Research, University Hospital of Basel, Basel CH-4031, Switzerland;Department of Surgery, Spitalzentrum, Biel CH-2502, Switzerland;Department of Surgery, Stadtspital Triemli, Zurich CH-8063, Switzerland;Swiss Group for Clinical Cancer Research (SAKK) (a member of the Swiss Institute for Applied Cancer Research, SIAK), Bern CH-3008, Switzerland;

关键词: Prognostic;    predictive;    colorectal cancer;    TGF-β;    SMAD;   

DOI  :  10.1593/neo.03442

来源: DOAJ

【 摘 要 】

BACKGROUND: Improved risk stratification of early colorectal cancer might help to better select patients for adjuvant treatment. Alterations in the transforming growth factor-β (TGIF-β) pathway have frequently been found in colorectal cancer, but their impact on prognosis remains controversial. We therefore analyzed two transcriptional corepressors of the TGF-β signaling pathway with respect to prognosis and prediction of chemotherapy benefit in early colorectal cancer. METHODS: The gene copy status of SKI and SNON was analyzed by use of quantitative real-time polymerase chain reaction in 179 colorectal tumor biopsies, which had been collected from a randomized multicenter trial of the Swiss Group for Clinical Cancer Research (SAKK). RESULTS: Partial or complete allelic loss was found in 41.5% and 55.2% for SKI and SNON, whereas amplification was found in 10.1% and 15.1%, respectively. Multivariate Cox analysis showed that gene amplification of SKI independently predicted reduced relapse-free [hazard ratio (HR) for relapse 2.08, P = .049] and overall survival (HR for death 2.62, P =.012). In contrast, deletion of SKI and the gene copy status of SNON were not significantly correlated with prognosis. CONCLUSION: Amplification of SKI is a negative prognostic marker in early-stage colorectal cancer. This marker should help to improve risk stratification to better select patients for adjuvant therapy. Confirmatory investigations are warranted.

【 授权许可】

Unknown