Tumor microenvironment and mitotic checkpoint are key factors in the outcome of classic Hodgkin lymphoma.
Around 20% to 30% of patients with Hodgkin lymphoma (HL) do not benefit from standard therapies and finally succumb to their disease. The factors that influence the outcome of HL have not been elucidated, underscoring the demand for the identification of biologic risk factors and new therapeutic targets. We analyzed the gene expression profiles of samples from 29 patients with advanced classic HL treated with standard therapy and compared the expression profiles of patients with favorable and unfavorable clinical outcome. Using supervised methods, we identified 145 genes associated with outcome, which were grouped into 4 signatures representing genes expressed by either the tumoral cells (genes involved in the regulation of mitosis and cell growth/apoptosis) or the tumor microenvironment. The relationship between the expression of 8 representative genes and survival was successfully validated in an independent series of 235 patients by quantification of protein expression levels on tissue microarrays. Analysis of centrosomes and mitotic checkpoint confirmed the existence of an abnormal transition through mitosis in HL cells. Therefore, genes related to tumor microenvironment, cell growth/apoptosis, and regulation of mitosis are associated with treatment response and outcome of patients with HL.
Sánchez-Aguilera
Abel
A
the Tumor Bank Network and the Histology and Immunohistochemistry Unit, Spanish National Cancer Centre (CNIO), Madrid.
Montalbán
Carlos
C
de la Cueva
Paloma
P
Sánchez-Verde
Lydia
L
Morente
Manuel M
MM
García-Cosío
Mónica
M
García-Laraña
José
J
Bellas
Carmen
C
Provencio
Mariano
M
Romagosa
Vicens
V
de Sevilla
Alberto Fernández
AF
Menárguez
Javier
J
Sabín
Pilar
P
Mestre
María J
MJ
Méndez
Miguel
M
Fresno
Manuel F
MF
Nicolás
Concepción
C
Piris
Miguel A
MA
García
Juan F
JF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D018385:Centrosome; D005260:Female; D020869:Gene Expression Profiling; D006689:Hodgkin Disease / Q000453:epidemiology / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics*; D011379:Prognosis; D011506:Proteins / Q000032:analysis / Q000235:genetics; D015996:Survival Rate; D016896:Treatment Outcome
D011506:Proteins