Exploring new prognostic biomarkers in Mantle Cell Lymphoma: a comparison of the circSCORE and the MCL35 score

Abstract

Mantle cell lymphoma (MCL) is a biologically and clinically heterogeneous disease, emphasizing the need for prognostic biomarkers. In this study we aimed at comparing the prognostic value of two RNA-based risk scores, circSCORE and MCL35, in 149 patients from the MCL2 (ISRCTN87866680) and MCL3 (NCT00514475) patient cohorts. Both risk scores provided significant stratification of high versus low risk for progression free survival (PFS) and overall survival (OS). The circSCORE retained significant prognostic value in adjusted multivariable Cox regressions for PFS, but not for OS. Furthermore, circSCORE added significant prognostic value to MIPI in the pooled cohort (MCL2 and MCL3) for PFS and OS, and for PFS in MCL3 alone, outperforming Ki67 and MCL35. We suggest a new, combined MIPI-circSCORE with improved prognostic value, and with potential for future clinical implementation, if validated in a larger, independent cohort.

Keywords:

• Mantle cell lymphoma
• circSCORE
• MCL35
• circRNA
• mRNA
• prognostic biomarkers

Acknowledgements

We express our gratitude to the Nordic Lymphoma Group (NLG) and to the patients participating in the MCL2 and MCL3 clinical trials for their important contributions to this study.

Author contributions

Conceived and designed the experiments: SH, CWE, LSK, MD, KG Performed the experiments: SH, CWE, MD, LSK. Analyzed the data: RS, MD, LSK, KG Contributed with patient material/reagents/materials/analysis tools: SH CWE, DWS, HH, AK, RR, SE, MJ, CG, LSK, MD, KG Wrote the paper: RS, MD.

All authors read and approved the final manuscript.

Disclosure statement

DWS is a named inventor on patents that describe using gene expression for subtyping aggressive B-cell lymphomas. CWE is currently employed in Genmab A/S. The remaining authors report there are no competing interests to declare.

Additional information

Funding

This work was supported by Rigshospitalet Research Foundation under Grant E-23718-16, The Novo Nordisk Foundation under Grant NNF17OC0029596, Amalie Jørgensen’s Memorial Grant, and Anita and Tage Therkelsen’s fund. KG is funded by a center grant from The Danish Cancer Society [Danish Research Center for Precision Medicine in Blood Cancer: Grant 223-A13071-18-S68], the Novo Nordisk Foundation [Novo Nordisk Foundation Center for Stem Cell Biology, DanStem: Grant NNF17CC0027852] and Greater Copenhagen Health Science Partners (Clinical Academic Group in Blood Cancers). LSK is funded by the Lundbeck Foundation [R307-2018-3433].