Gene-expression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5′fluoruracil-based adjuvant chemotherapy
María Dolores Giráldez
Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorJuan José Lozano
Bioinformatics Unit, CIBERehd, Barcelona, Catalonia, Spain
Search for more papers by this authorMíriam Cuatrecasas
Department of Pathology, Hospital Clínic, CIBERehd, IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorVirginia Alonso-Espinaco
Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorJoan Maurel
Department of Medical Oncology, Hospital Clínic, CIBERehd, IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorMaribel Mármol
Department of Medical Oncology, Hospital Clínic, CIBERehd, IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorCarlos Hörndler
Department of Pathology, Hospital Miguel Servet, Zaragoza, Spain
Search for more papers by this authorJavier Ortego
Department of Pathology, Hospital Clínico Lozano Blesa, Zaragoza, Spain
Search for more papers by this authorVicente Alonso
Department of Medical Oncology, Hospital Miguel Servet, Zaragoza, Spain
Search for more papers by this authorPilar Escudero
Medical Oncology Departments, Hospital Clínico Lozano Blesa, Zaragoza, Spain
Search for more papers by this authorGina Ramírez
Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorAurea Mira
Center for Biomedical Diagnosis, Hospital Clínic, CIBERehd, IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorCorresponding Author
Antoni Castells
Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Tel.: +34-93-227-5739, Fax: +34-93-227-5589
Department of Gastroenterology, Hospital Clínic, Villarroel 170, 08036 Barcelona, Catalonia, SpainSearch for more papers by this authorMaría Dolores Giráldez
Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorJuan José Lozano
Bioinformatics Unit, CIBERehd, Barcelona, Catalonia, Spain
Search for more papers by this authorMíriam Cuatrecasas
Department of Pathology, Hospital Clínic, CIBERehd, IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorVirginia Alonso-Espinaco
Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorJoan Maurel
Department of Medical Oncology, Hospital Clínic, CIBERehd, IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorMaribel Mármol
Department of Medical Oncology, Hospital Clínic, CIBERehd, IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorCarlos Hörndler
Department of Pathology, Hospital Miguel Servet, Zaragoza, Spain
Search for more papers by this authorJavier Ortego
Department of Pathology, Hospital Clínico Lozano Blesa, Zaragoza, Spain
Search for more papers by this authorVicente Alonso
Department of Medical Oncology, Hospital Miguel Servet, Zaragoza, Spain
Search for more papers by this authorPilar Escudero
Medical Oncology Departments, Hospital Clínico Lozano Blesa, Zaragoza, Spain
Search for more papers by this authorGina Ramírez
Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorAurea Mira
Center for Biomedical Diagnosis, Hospital Clínic, CIBERehd, IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Search for more papers by this authorCorresponding Author
Antoni Castells
Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain
Tel.: +34-93-227-5739, Fax: +34-93-227-5589
Department of Gastroenterology, Hospital Clínic, Villarroel 170, 08036 Barcelona, Catalonia, SpainSearch for more papers by this authorAbstract
Although receiving adjuvant chemotherapy after radical surgery, a disappointing proportion of patients with colorectal cancer will develop tumor recurrence. Probability of relapse is currently predicted from pathological staging, there being a need for additional markers to further select high-risk patients. This study was aimed to identify a gene-expression signature to predict tumor recurrence in patients with Stages II and III colon cancer treated with 5′fluoruracil (5FU)-based adjuvant chemotherapy. Two-hundred and twenty-eight patients diagnosed with Stages II–III colon cancer and treated with surgical resection and 5FU-based adjuvant chemotherapy were included. RNA was extracted from formalin-fixed, paraffin-embedded tissue samples and expression of 27 selected candidate genes was analyzed by RT-qPCR. A tumor recurrence predicting model, including clinico-pathological variables and gene-expression profiling, was developed by Cox regression analysis and validated by bootstrapping. The regression analysis identified tumor stage and S100A2 and S100A10 gene expression as independently associated with tumor recurrence. The risk score derived from this model was able to discriminate two groups with a highly significant different probability of tumor recurrence (HR, 2.75; 95%CI, 1.71–4.39; p = 0.0001), which it was maintained when patients were stratified according to tumor stage. The algorithm was also able to distinguish two groups with different overall survival (HR, 2.68; 95%CI, 1.12–6.42; p = 0.03). Identification of a new gene-expression signature associated with a high probability of tumor recurrence in patients with Stages II and III colon cancer receiving adjuvant 5FU-based chemotherapy, and its combination in a robust, easy-to-use and reliable algorithm may contribute to tailor treatment and surveillance strategies.
Abstract
What's new?
A disappointing proportion of patients with colon cancer who received adjuvant chemotherapy after radical surgery will nonetheless develop tumor recurrence. Patients' chances of relapse are currently being predicted using pathological staging, and additional markers are needed to help select high-risk patients. This study identified a new gene-expression signature that, along with tumor stage, provides a robust and easy-to-use and reliable mathematical algorithm to identify patients at higher risk of tumor relapse and shorter survival who may eventually benefit from a more aggressive therapeutic regimen and more intensive surveillance.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
|---|---|
| IJC_27747_sm_SuppTab1.doc47 KB | Supporting Information Table 1. Candidate genes evaluated in the analysis. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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