title: Gene-expression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5'fluoruracil-based adjuvant chemotherapy.
abstract: 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.
authors: Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, IDIBAPS*, University of Barcelona, Barcelona, Catalonia, Spain.
authors: María Dolores
authors: MD
authors: Giráldez
authors: Juan José
authors: JJ
authors: Lozano
authors: Míriam
authors: M
authors: Cuatrecasas
authors: Virginia
authors: V
authors: Alonso-Espinaco
authors: Joan
authors: J
authors: Maurel
authors: Maribel
authors: M
authors: Mármol
authors: Carlos
authors: C
authors: Hörndler
authors: Javier
authors: J
authors: Ortego
authors: Vicente
authors: V
authors: Alonso
authors: Pilar
authors: P
authors: Escudero
authors: Gina
authors: G
authors: Ramírez
authors: Christoph
authors: C
authors: Petry
authors: Luis
authors: L
authors: Lasalvia
authors: Kerstin
authors: K
authors: Bohmann
authors: Ralph
authors: R
authors: Wirtz
authors: Aurea
authors: A
authors: Mira
authors: Antoni
authors: A
authors: Castells
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D059467:Transcriptome
chemical_list: D005472:Fluorouracil