Stage II colon cancer prognosis prediction by tumor gene expression profiling.
OBJECTIVE
This study mainly aimed to identify and assess the performance of a microarray-based prognosis predictor (PP) for stage II colon cancer. A previously suggested 23-gene prognosis signature (PS) was also evaluated.


METHODS
Tumor mRNA samples from 50 patients were profiled using oligonucleotide microarrays. PPs were built and assessed by random divisions of patients into training and validation sets (TSs and VSs, respectively). For each TS/VS split, a 30-gene PP, identified on the TS by selecting the 30 most differentially expressed genes and applying diagonal linear discriminant analysis, was used to predict the prognoses of VS patients. Two schemes were considered: single-split validation, based on a single random split of patients into two groups of equal size (group 1 and group 2), and Monte Carlo cross validation (MCCV), whereby patients were repeatedly and randomly divided into TS and VS of various sizes.


RESULTS
The 30-gene PP, identified from group 1 patients, yielded an 80% prognosis prediction accuracy on group 2 patients. MCCV yielded the following average prognosis prediction performance measures: 76.3% accuracy, 85.1% sensitivity, and 67.5% specificity. Improvements in prognosis prediction were observed with increasing TS size. The 30-gene PS were found to be highly-variable across TS/VS splits. Assessed on the same random splits of patients, the previously suggested 23-gene PS yielded a 67.7% mean prognosis prediction accuracy.


CONCLUSIONS
Microarray gene expression profiling is able to predict the prognosis of stage II colon cancer patients. The present study also illustrates the usefulness of resampling techniques for honest performance assessment of microarray-based PPs.
Barrier
Alain
A
Service de Chirurgie digestive, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, France. alain.barrier@tnn.ap-hop-paris.fr
Boelle
Pierre-Yves
PY
Roser
François
F
Gregg
Jennifer
J
Tse
Chantal
C
Brault
Didier
D
Lacaine
François
F
Houry
Sidney
S
Huguier
Michel
M
Franc
Brigitte
B
Flahault
Antoine
A
Lemoine
Antoinette
A
Dudoit
Sandrine
S
D000368:Aged; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D009010:Monte Carlo Method; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D011897:Random Allocation; D012680:Sensitivity and Specificity