Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells.
BACKGROUND
Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival.


METHODS
Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens.


RESULTS
Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells.


CONCLUSIONS
The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.
Dave
Sandeep S
SS
National Cancer Institute, NIH, Bethesda, Md 20892, USA.
Wright
George
G
Tan
Bruce
B
Rosenwald
Andreas
A
Gascoyne
Randy D
RD
Chan
Wing C
WC
Fisher
Richard I
RI
Braziel
Rita M
RM
Rimsza
Lisa M
LM
Grogan
Thomas M
TM
Miller
Thomas P
TP
LeBlanc
Michael
M
Greiner
Timothy C
TC
Weisenburger
Dennis D
DD
Lynch
James C
JC
Vose
Julie
J
Armitage
James O
JO
Smeland
Erlend B
EB
Kvaloy
Stein
S
Holte
Harald
H
Delabie
Jan
J
Connors
Joseph M
JM
Lansdorp
Peter M
PM
Ouyang
Qin
Q
Lister
T Andrew
TA
Davies
Andrew J
AJ
Norton
Andrew J
AJ
Muller-Hermelink
H Konrad
HK
Ott
German
G
Campo
Elias
E
Montserrat
Emilio
E
Wilson
Wyndham H
WH
Jaffe
Elaine S
ES
Simon
Richard
R
Yang
Liming
L
Powell
John
J
Zhao
Hong
H
Goldschmidt
Neta
N
Chiorazzi
Michael
M
Staudt
Louis M
LM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D003713:Dendritic Cells / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D008224:Lymphoma, Follicular / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis