Stromal gene signatures in large-B-cell lymphomas.
BACKGROUND
The addition of rituximab to combination chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or R-CHOP, has significantly improved the survival of patients with diffuse large-B-cell lymphoma. Whether gene-expression signatures correlate with survival after treatment of diffuse large-B-cell lymphoma is unclear.


METHODS
We profiled gene expression in pretreatment biopsy specimens from 181 patients with diffuse large-B-cell lymphoma who received CHOP and 233 patients with this disease who received R-CHOP. A multivariate gene-expression-based survival-predictor model derived from a training group was tested in a validation group.


RESULTS
A multivariate model created from three gene-expression signatures--termed "germinal-center B-cell," "stromal-1," and "stromal-2"--predicted survival both in patients who received CHOP and patients who received R-CHOP. The prognostically favorable stromal-1 signature reflected extracellular-matrix deposition and histiocytic infiltration. By contrast, the prognostically unfavorable stromal-2 signature reflected tumor blood-vessel density.


CONCLUSIONS
Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment.
Lenz
G
G
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Wright
G
G
Dave
S S
SS
Xiao
W
W
Powell
J
J
Zhao
H
H
Xu
W
W
Tan
B
B
Goldschmidt
N
N
Iqbal
J
J
Vose
J
J
Bast
M
M
Fu
K
K
Weisenburger
D D
DD
Greiner
T C
TC
Armitage
J O
JO
Kyle
A
A
May
L
L
Gascoyne
R D
RD
Connors
J M
JM
Troen
G
G
Holte
H
H
Kvaloy
S
S
Dierickx
D
D
Verhoef
G
G
Delabie
J
J
Smeland
E B
EB
Jares
P
P
Martinez
A
A
Lopez-Guillermo
A
A
Montserrat
E
E
Campo
E
E
Braziel
R M
RM
Miller
T P
TP
Rimsza
L M
LM
Cook
J R
JR
Pohlman
B
B
Sweetenham
J
J
Tubbs
R R
RR
Fisher
R I
RI
Hartmann
E
E
Rosenwald
A
A
Ott
G
G
Muller-Hermelink
H-K
HK
Wrench
D
D
Lister
T A
TA
Jaffe
E S
ES
Wilson
W H
WH
Chan
W C
WC
Staudt
L M
LM
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols; D003520:Cyclophosphamide; D018450:Disease Progression; D004317:Doxorubicin; D005109:Extracellular Matrix / Q000235:genetics; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005802:Genes, MHC Class II; D018858:Germinal Center; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000235:genetics; D011241:Prednisone; D011379:Prognosis; D000069283:Rituximab; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D014750:Vincristine
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone