Generation and external validation of a tumor-derived 5-gene prognostic signature for recurrence of lymph node-negative, invasive colorectal carcinoma

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  author =       "Peter F. Lenehan and Lisa A. Boardman and 
                 Douglas Riegert-Johnson and Giovanni {De Petris} and 
                 David W. Fry and Jeanne Ohrnberger and Eugene R. Heyman and 
                 Brigitte Gerard and Arpit A. Almal and 
                 William P. Worzel",
  title =        "Generation and external validation of a tumor-derived
                 5-gene prognostic signature for recurrence of lymph
                 node-negative, invasive colorectal carcinoma",
  journal =      "Cancer",
  year =         "2012",
  volume =       "118",
  number =       "21",
  pages =        "5234--5244",
  month =        "1 " # nov,
  keywords =     "genetic algorithms, genetic programming, colorectal
                 cancer, gene expression signatures, machine learning,
                 recurrence, reverse transcriptase-polymerase chain
                 reaction, prognosis, validation studies, sensitivity
                 and specificity, colonic polyps.",
  ISSN =         "1097-0142",
  organization = "American Cancer Society",
  DOI =          "doi:10.1002/cncr.27628",
  size =         "11 pages",
  abstract =     "BACKGROUND: One in 4 patients with lymph
                 node-negative, invasive colorectal carcinoma (CRC)
                 develops recurrent disease after undergoing curative
                 surgery, and most die of advanced disease. Predicting
                 which patients will develop a recurrence is a
                 significantly growing, unmet medical need.

                 METHODS: Archival formalin-fixed, paraffin-embedded
                 (FFPE) primary adenocarcinoma tissues obtained at
                 surgery were retrieved from 74 patients with CRC (15
                 with stage I disease and 59 with stage II disease) for
                 Training/Test Sets. In addition, FFPE tissues were
                 retrieved from 49 patients with stage I CRC and 215
                 patients with stage II colon cancer for an External
                 Validation (EV) Set (n=264) from 18 hospitals in 4
                 countries. No patients had received
                 neoadjuvant/adjuvant therapy. Proprietary genetic
                 programming analysis of expression profiles for 225
                 prespecified tumour genes was used to create a 36-month
                 recurrence risk signature.

                 RESULTS: Using reverse transcriptase-polymerase chain
                 reaction, a 5-gene rule correctly classified 62 of 92
                 recurrent patients and 87 of 172 nonrecurrent patients
                 in the EV Set (sensitivity, 0.67; specificity, 0.51).
                 High-risk patients had a greater probability of
                 36-month recurrence (42percent) than low-risk patients
                 (26percent; hazard ratio, 1.80; 95percent confidence
                 interval, 1.19-2.71; P=0.007; Cox regression)
                 independent of T-classification, the number of lymph
                 nodes examined, histologic grade/subtype, anatomic
                 location, age, sex, or race. The rule outperformed
                 (P=0.021) current National Comprehensive Cancer Network
                 Guidelines (hazard ratio, 0.897). The same rule also
                 differentiated the risk of recurrence (hazard ratio,
                 1.63; P=0.031) in a subset of patients from the EV Set
                 who had stage I/II colon cancer only

                 CONCLUSIONS: the 5-gene rule (OncoDefender-CRC) is the
                 first molecular prognostic that has been validated in
                 both stage I CRC and stage II colon cancer. It
                 outperforms standard clinicopathologic prognostic
                 criteria and obviates the need to retrieve >= 12 lymph
                 nodes for accurate prognostication. It identifies those
                 patients most likely to develop recurrent disease
                 within 3 years after curative surgery and, thus, those
                 most likely to benefit from adjuvant treatment.",
  notes =        "PMID: PMC3532613

Genetic Programming entries for Peter F Lenehan Lisa A Boardman Douglas Riegert-Johnson Giovanni De Petris David W Fry Jeanne Ohrnberger Eugene R Heyman Brigitte Gerard Arpit A Almal William P Worzel