Expression patterns and prognostic potential of circular RNAs in mantle cell lymphoma: a study of younger patients from the MCL2 and MCL3 clinical trials

Mette Dahl, Simon Husby, Christian Winther Eskelund, Søren Besenbacher, Søren Fjelstrup, Christophe Côme, Sara Ek, Arne Kolstad, Riikka Räty, Mats Jerkeman, Christian H Geisler, Jørgen Kjems, Lasse Sommer Kristensen*, Kirsten Grønbæk

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Mantle cell lymphoma (MCL) is characterized by marked differences in outcome, emphasizing the need for strong prognostic biomarkers. Here, we explore expression patterns and prognostic relevance of circular RNAs (circRNAs), a group of endogenous non-coding RNA molecules, in MCL. We profiled the circRNA expression landscape using RNA-sequencing and explored the prognostic potential of 40 abundant circRNAs in samples from the Nordic MCL2 and MCL3 clinical trials, using NanoString nCounter Technology. We report a circRNA-based signature (circSCORE) developed in the training cohort MCL2 that is highly predictive of time to progression (TTP) and lymphoma-specific survival (LSS). The dismal outcome observed in the large proportion of patients assigned to the circSCORE high-risk group was confirmed in the independent validation cohort MCL3, both in terms of TTP (HR 3.0; P = 0.0004) and LSS (HR 3.6; P = 0.001). In Cox multiple regression analysis incorporating MIPI, Ki67 index, blastoid morphology and presence of TP53 mutations, circSCORE retained prognostic significance for TTP (HR 3.2; P = 0.01) and LSS (HR 4.6; P = 0.01). In conclusion, circRNAs are promising prognostic biomarkers in MCL and circSCORE improves identification of high-risk disease among younger patients treated with cytarabine-containing chemoimmunotherapy and autologous stem cell transplant.

Original languageEnglish
JournalLeukemia
Volume36
Issue1
Pages (from-to)177-188
Number of pages12
ISSN0887-6924
DOIs
Publication statusPublished - Jan 2022

Keywords

  • 15-YEAR FOLLOW-UP
  • BIOGENESIS
  • CARCINOMA
  • CIRC-ZNF609
  • CYTOLOGY
  • GENE-EXPRESSION
  • IMMUNOCHEMOTHERAPY
  • PROGRESSION
  • SIGNATURE
  • SURVIVAL

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