Identification of biological markers of sensitivity to high-clinical-risk-adapted therapy for patients with diffuse large B-cell lymphoma.
The aim of the project was to identify biological variables in high-clinical-risk patients with diffuse large B-cell lymphoma (DLBCL), treated with risk-adapted therapies. The study was performed in a series of high-clinical-risk patients with DLBCL treated with MegaCHOP or MegaCHOP + IFE followed by autologous stem-cell transplantation (ASCT). An initial reduced set of diagnostic tumoral samples was studied by gene expression profiling and gene-set-enrichment analysis. A set of potential biomarkers extracted from this study was then explored in tissue microarrays containing paraffin-diagnostic tissue from 50 patients. The statistical analysis identified 17 immunohistochemical markers associated with the clinical endpoints. A subsequent multivariate analysis identified FoxP3+ T-reg cells as an independent predictor of failure-free survival. Bcl6 expression, CG/ABC subclasses and IPI were found not to predict survival in this series. The increased presence of regulatory T-cells as a marker of adverse outcome highlights specific components of the tumoral microenvironment in the pathogenesis and treatment response prediction for high-clinical-risk patients with DLBCL.
Saez
Ana I
AI
Red de Bancos de Tumores de Andalucia, Granada, Spain. anai.saez.exts@juntadeandalucia.es
García-Cosío
Mónica
M
Sáez
Antonio J
AJ
Hernández
Jesús M
JM
Sánchez-Verde
Lidia
L
Alvarez
David
D
de la Cueva
Paloma
P
Arranz
Reyes
R
Conde
Eulogio
E
Grande
Carlos
C
Rodríguez
José
J
Caballero
Dolores
D
Piris
Miguel A
MA
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D033581:Stem Cell Transplantation / Q000379:methods*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors