title: Gene expression signature to improve prognosis prediction of stage II and III colorectal cancer.
abstract: OBJECTIVE
  This study aims to develop a robust gene expression classifier that can predict disease relapse in patients with early-stage colorectal cancer (CRC).
  
  
  METHODS
  Fresh frozen tumor tissue from 188 patients with stage I to IV CRC undergoing surgery was analyzed using Agilent 44K oligonucleotide arrays. Median follow-up time was 65.1 months, and the majority of patients (83.6%) did not receive adjuvant chemotherapy. A nearest mean classifier was developed using a cross-validation procedure to score all genes for their association with 5-year distant metastasis-free survival.
  
  
  RESULTS
  An optimal set of 18 genes was identified and used to construct a prognostic classifier (ColoPrint). The signature was validated on an independent set of 206 samples from patients with stage I, II, and III CRC. The signature classified 60% of patients as low risk and 40% as high risk. Five-year relapse-free survival rates were 87.6% (95% CI, 81.5% to 93.7%) and 67.2% (95% CI, 55.4% to 79.0%) for low- and high-risk patients, respectively, with a hazard ratio (HR) of 2.5 (95% CI, 1.33 to 4.73; P = .005). In multivariate analysis, the signature remained one of the most significant prognostic factors, with an HR of 2.69 (95% CI, 1.41 to 5.14; P = .003). In patients with stage II CRC, the signature had an HR of 3.34 (P = .017) and was superior to American Society of Clinical Oncology criteria in assessing the risk of cancer recurrence without prescreening for microsatellite instability (MSI).
  
  
  CONCLUSIONS
  ColoPrint significantly improves the prognostic accuracy of pathologic factors and MSI in patients with stage II and III CRC and facilitates the identification of patients with stage II disease who may be safely managed without chemotherapy.
authors.affiliation: Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Av Gran Via 199-203, Barcelona, Spain 08907. ramonsalazar@iconcologia.net
authors.forename: Ramon
authors.initials: R
authors.lastname: Salazar
authors.forename: Paul
authors.initials: P
authors.lastname: Roepman
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capella
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.forename: Iris
authors.initials: I
authors.lastname: Simon
authors.forename: Christa
authors.initials: C
authors.lastname: Dreezen
authors.forename: Adriana
authors.initials: A
authors.lastname: Lopez-Doriga
authors.forename: Cristina
authors.initials: C
authors.lastname: Santos
authors.forename: Corrie
authors.initials: C
authors.lastname: Marijnen
authors.forename: Johan
authors.initials: J
authors.lastname: Westerga
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Bruin
authors.forename: David
authors.initials: D
authors.lastname: Kerr
authors.forename: Peter
authors.initials: P
authors.lastname: Kuppen
authors.forename: Cornelis
authors.initials: C
authors.lastname: van de Velde
authors.forename: Hans
authors.initials: H
authors.lastname: Morreau
authors.forename: Loes
authors.initials: L
authors.lastname: Van Velthuysen
authors.forename: Annuska M
authors.initials: AM
authors.lastname: Glas
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Van't Veer
authors.forename: Rob
authors.initials: R
authors.lastname: Tollenaar
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies