Abstract | PURPOSE: RACGAP1 is a Rac GTPase-activating protein involved in cell growth regulation, cell transformation and metastasis. The aim of the present study was to explore the prognostic and/or predictive significance of RACGAP1 mRNA expression on disease-free survival (DFS) and overall survival (OS) in high-risk early breast cancer patients and compare it to that of Ki67 protein expression and to the Nottingham prognostic index (NPI). METHODS: A total of 595 high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative dose-dense sequential chemotherapy with epirubicin followed by CMF with or without paclitaxel. RNA was extracted from 314 formalin-fixed paraffin-embedded primary tumor tissue samples followed by one-step quantitative RT-PCR for assessing RACGAP1 mRNA expression. RESULTS: High RACGAP1 mRNA expression (above the median) was associated with poor DFS (log-rank, p = 0.002) and OS (p < 0.001). High histological grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of RACGAP1. Results of the Cox multivariate regression analysis revealed that high RACGAP1 mRNA expression independently predicted poor overall survival (Wald's p = 0.008). High Ki67 protein expression was also an adverse prognostic factor for death (p = 0.016), while high NPI score values were not. CONCLUSIONS: High RACGAP1 mRNA expression, as assessed by qRT-PCR, was found to be of adverse prognostic significance in high-risk early breast cancer patients treated with dose-dense sequential chemotherapy. The utility of RACGAP1 mRNA expression in patient selection for treatment with aggressive chemotherapy regimens should be further explored and validated in larger cohorts.
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Authors | K Pliarchopoulou, K T Kalogeras, R Kronenwett, R M Wirtz, A G Eleftheraki, A Batistatou, M Bobos, N Soupos, G Polychronidou, H Gogas, E Samantas, C Christodoulou, T Makatsoris, N Pavlidis, D Pectasides, G Fountzilas |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 71
Issue 1
Pg. 245-55
(Jan 2013)
ISSN: 1432-0843 [Electronic] Germany |
PMID | 23096218
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- GTPase-Activating Proteins
- Ki-67 Antigen
- RNA, Messenger
- mgcRacGAP
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Topics |
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, pharmacology)
- Breast Neoplasms
(drug therapy, genetics, pathology)
- Disease-Free Survival
- Female
- GTPase-Activating Proteins
(genetics)
- Gene Expression Regulation, Neoplastic
- Humans
- Ki-67 Antigen
(genetics)
- Middle Aged
- Multivariate Analysis
- Patient Selection
- Prognosis
- Proportional Hazards Models
- RNA, Messenger
(metabolism)
- Randomized Controlled Trials as Topic
- Regression Analysis
- Retrospective Studies
- Reverse Transcriptase Polymerase Chain Reaction
- Survival Rate
- Young Adult
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