title: Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells.
abstract: 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.
authors.affiliation: National Cancer Institute, NIH, Bethesda, Md 20892, USA.
authors.forename: Sandeep S
authors.initials: SS
authors.lastname: Dave
authors.forename: George
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authors.lastname: Wright
authors.forename: Bruce
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authors.lastname: Tan
authors.forename: Andreas
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authors.lastname: Rosenwald
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Richard I
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authors.lastname: Fisher
authors.forename: Rita M
authors.initials: RM
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authors.forename: Lisa M
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authors.lastname: Miller
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authors.lastname: LeBlanc
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authors.initials: TC
authors.lastname: Greiner
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: James C
authors.initials: JC
authors.lastname: Lynch
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authors.lastname: Vose
authors.forename: James O
authors.initials: JO
authors.lastname: Armitage
authors.forename: Erlend B
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authors.lastname: Smeland
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authors.lastname: Kvaloy
authors.forename: Harald
authors.initials: H
authors.lastname: Holte
authors.forename: Jan
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authors.lastname: Delabie
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Peter M
authors.initials: PM
authors.lastname: Lansdorp
authors.forename: Qin
authors.initials: Q
authors.lastname: Ouyang
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Lister
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Davies
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Norton
authors.forename: H Konrad
authors.initials: HK
authors.lastname: Muller-Hermelink
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Emilio
authors.initials: E
authors.lastname: Montserrat
authors.forename: Wyndham H
authors.initials: WH
authors.lastname: Wilson
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Richard
authors.initials: R
authors.lastname: Simon
authors.forename: Liming
authors.initials: L
authors.lastname: Yang
authors.forename: John
authors.initials: J
authors.lastname: Powell
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Neta
authors.initials: N
authors.lastname: Goldschmidt
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authors.lastname: Chiorazzi
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authors.lastname: Staudt
mesh_terms: 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