Predicting outcome in follicular lymphoma by using interactive gene pairs.
OBJECTIVE
Follicular lymphoma is a common lymphoma of adults. Although its course is often indolent, a substantial proportion of patients have a poor prognosis, often due to rapid progression or transformation to a more aggressive lymphoma. Currently available clinical prognostic scores, such as the follicular lymphoma international prognostic index, are not able to optimally predict transformation or poor outcome.


METHODS
Gene expression profiling was done on primary lymphoma biopsy samples.


RESULTS
Using a statistically conservative approach, predictive interaction analysis, we have identified pairs of interacting genes that predict poor outcome, measured as death within 5 years of diagnosis. The best gene pair performs >1,000-fold better than any single gene or the follicular lymphoma international prognostic index in our data set. Many gene pairs achieve outcome prediction accuracies exceeding 85% in extensive cross-validation and noise sensitivity computational analyses. Many genes repeatedly appear in top-ranking pairs, suggesting that they reproducibly provide predictive capability.


CONCLUSIONS
The evidence reported here may provide the basis for an expression-based, multi-gene test for predicting poor follicular lymphoma outcomes.
LeBrun
David
D
Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada.
Baetz
Tara
T
Foster
Cheryl
C
Farmer
Patricia
P
Sidhu
Roger
R
Guo
Hong
H
Harrison
Karen
K
Somogyi
Roland
R
Greller
Larry D
LD
Feilotter
Harriet
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis