MicroRNA signatures and treatment response in patients with advanced classical Hodgkin lymphoma

Beatriz Sánchez-Espiridión, Ana M. Martín-Moreno, Carlos Montalbán, Vianihuini Figueroa, Francisco Vega, Anas Younes, L. Jeffrey Medeiros, Francisco J. Alvés, Miguel Canales, Mónica Estévez, Javier Menarguez, Pilar Sabín, María C. Ruiz-Marcellán, Andrés Lopez, Pedro Sánchez-Godoy, Fernando Burgos, Carlos Santonja, José L. López, Miguel A. Piris, Juan F. Garcia

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Although specific microRNA (miRNA) signatures in classical Hodgkin lymphoma (cHL) have been proposed, their relationship with clinical outcome remains unclear. Despite treatment advances, a substantial subset of patients with advanced cHL are refractory to standard therapies based on adriamycin and its variants. Global miRNA expression data of 29 advanced cHL patients and five cHL-derived cell lines were used to identify profiles from Hodgkin-Reed-Sternberg (HRS) cells and their non-tumoural microenvironment. A cHL-miRNA signature was identified with 234 miRNAs differentially expressed. A subset of these miRNAs was associated with outcome and selected for study in an independent set of 168 cHL samples using quantitative reverse transcription polymerase chain reaction. Multivariate Cox regression analyses including cross-validation with failure-free survival (FFS) as clinical endpoint revealed a miRNA signature with MIR21, MIR30E, MIR30D and MIR92B*that identified two risk-groups with significant differences in 5-year FFS (81% vs. 35·7%; P < 0·001). Additionally, functional silencing of MIR21 and MIR30D in L428 cells showed increased sensitivity to doxorubicin-induced apoptosis, pointing towards abnormalities of mitochondrial intrinsic and TP53-CDKN1A pathways as related to miRNA deregulation in cHL. These results suggest that clinical outcome in cHL is associated with a specific miRNA signature. Moreover, functional analyses suggest a role for MIR21 and MIR30D in cHL pathogenesis and therapeutic resistance.

Original languageEnglish (US)
Pages (from-to)336-347
Number of pages12
JournalBritish Journal of Haematology
Volume162
Issue number3
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

Keywords

  • Clinical outcome
  • Hodgkin lymphoma
  • MicroRNA
  • Molecular pathogenesis
  • RT-polymerase chain reaction

ASJC Scopus subject areas

  • Hematology

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  • Cite this

    Sánchez-Espiridión, B., Martín-Moreno, A. M., Montalbán, C., Figueroa, V., Vega, F., Younes, A., Medeiros, L. J., Alvés, F. J., Canales, M., Estévez, M., Menarguez, J., Sabín, P., Ruiz-Marcellán, M. C., Lopez, A., Sánchez-Godoy, P., Burgos, F., Santonja, C., López, J. L., Piris, M. A., & Garcia, J. F. (2013). MicroRNA signatures and treatment response in patients with advanced classical Hodgkin lymphoma. British Journal of Haematology, 162(3), 336-347. https://doi.org/10.1111/bjh.12390