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

Dahl, Mette ; Husby, Simon ; Eskelund, Christian W. ; Besenbacher, Søren ; Fjelstrup, Søren ; Côme, Christophe ; Ek, Sara LU ; Kolstad, Arne ; Räty, Riikka and Jerkeman, Mats LU , et al. (2022) In Leukemia 36(1). p.177-188
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Leukemia
volume
36
issue
1
pages
177 - 188
publisher
Nature Publishing Group
external identifiers
  • scopus:85110020749
  • pmid:34244612
ISSN
0887-6924
DOI
10.1038/s41375-021-01311-4
language
English
LU publication?
yes
id
b37263d5-1f3e-4dd0-9c05-9347f6033859
date added to LUP
2021-12-23 14:35:30
date last changed
2024-06-15 23:17:14
@article{b37263d5-1f3e-4dd0-9c05-9347f6033859,
  abstract     = {{<p>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.</p>}},
  author       = {{Dahl, Mette and Husby, Simon and Eskelund, Christian W. and Besenbacher, Søren and Fjelstrup, Søren and Côme, Christophe and Ek, Sara and Kolstad, Arne and Räty, Riikka and Jerkeman, Mats and Geisler, Christian H. and Kjems, Jørgen and Kristensen, Lasse S. and Grønbæk, Kirsten}},
  issn         = {{0887-6924}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{177--188}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Leukemia}},
  title        = {{Expression patterns and prognostic potential of circular RNAs in mantle cell lymphoma : a study of younger patients from the MCL2 and MCL3 clinical trials}},
  url          = {{http://dx.doi.org/10.1038/s41375-021-01311-4}},
  doi          = {{10.1038/s41375-021-01311-4}},
  volume       = {{36}},
  year         = {{2022}},
}