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Gene‐expression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5′fluoruracil‐based adjuvant chemotherapy
Author(s) -
Giráldez María Dolores,
Lozano Juan José,
Cuatrecasas Míriam,
AlonsoEspinaco Virginia,
Maurel Joan,
Mármol Maribel,
Hörndler Carlos,
Ortego Javier,
Alonso Vicente,
Escudero Pilar,
Ramírez Gina,
Petry Christoph,
LaSalvia Luis,
Bohmann Kerstin,
Wirtz Ralph,
Mira Aurea,
Castells Antoni
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27747
Subject(s) - medicine , colorectal cancer , oncology , pathological , proportional hazards model , chemotherapy , stage (stratigraphy) , gene signature , cancer , pathology , gene expression , gene , biology , paleontology , biochemistry
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.