- 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 (n=251).
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 http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%291097-0142",
