期刊
LEUKEMIA
卷 36, 期 1, 页码 177-188出版社
SPRINGERNATURE
DOI: 10.1038/s41375-021-01311-4
关键词
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资金
- Rigshospitalets Research foundation
- Novo Nordisk Foundation [NNF17OC0029596]
- Lundbeck Foundation [R307-2018-3433]
- Mindegaard Donationen, Rigshospitalet
- Sejer Persson & Lis Kluver Persson's fund
- Danish Cancer Society (Danish Research Center for Precision Medicine in Blood Cancer) [223-A13071-18-S68]
- Novo Nordisk Foundation (Novo Nordisk Foundation Center for Stem Cell Biology, DanStem) [NNF17CC0027852]
- Greater Copenhagen Health Science Partners (Clinical Academic Group in Blood Cancers)
Circular RNAs (circRNAs) show promise as prognostic biomarkers in mantle cell lymphoma (MCL); the circSCORE signature improves the identification of high-risk disease in younger patients receiving cytarabine-containing chemoimmunotherapy and autologous stem cell transplant.
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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