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

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.

Husby, SimonCopenhagen University Hospital,University of Copenhagen (author)
Eskelund, Christian W.University of Copenhagen,Copenhagen University Hospital (author)
Besenbacher, SørenAarhus University (author)
Fjelstrup, SørenAarhus University (author)
Côme, ChristopheUniversity of Copenhagen,Copenhagen University Hospital (author)
Ek, SaraLund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)immt-san (author)
Kolstad, ArneNorwegian Radium Hospital (author)
Räty, RiikkaHelsinki University Central Hospital (author)
Jerkeman, MatsLund University,Lunds universitet,Lymfom - Klinisk forskning,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Lymphoma - Clinical Research,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments(Swepub:lu)onk-mje (author)
Geisler, Christian H.Copenhagen University Hospital (author)
Kjems, JørgenAarhus University (author)
Kristensen, Lasse S.Aarhus University (author)
Grønbæk, KirstenUniversity of Copenhagen,Copenhagen University Hospital (author)
University of CopenhagenCopenhagen University Hospital (creator_code:org_t)

In:Leukemia: Springer Science and Business Media LLC36:1, s. 177-1880887-69241476-5551

By the author/editor: Dahl, Mette; Husby, Simon; Eskelund, Christ ...; Besenbacher, Sør ...; Fjelstrup, Søren; Côme, Christophe; show more...; Ek, Sara; Kolstad, Arne; Räty, Riikka; Jerkeman, Mats; Geisler, Christi ...; Kjems, Jørgen; Kristensen, Lass ...; Grønbæk, Kirsten; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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