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Development and Val...
Development and Validation of a Novel RNA Sequencing-Based Prognostic Score for Acute Myeloid Leukemia
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- Wang, Mei (författare)
- Karolinska Inst, Dept Med Epidemiol & Biostat, POB 281, SE-17177 Stockholm, Sweden
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- Lindberg, Johan (författare)
- Karolinska Institutet
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- Klevebring, Daniel (författare)
- Karolinska Inst, Dept Med Epidemiol & Biostat, POB 281, SE-17177 Stockholm, Sweden
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- Nilsson, Christer (författare)
- Karolinska Institutet
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- Lehmann, Sören (författare)
- Karolinska Institutet,Uppsala universitet,Hematologi,Karolinska Univ Hosp, Hematol Ctr, Stockholm, Sweden;Karolinska Inst, Dept Med, Huddinge, Sweden
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- Grönberg, Henrik (författare)
- Karolinska Institutet
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- Rantalainen, Mattias (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2018-03-01
- 2018
- Engelska.
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Ingår i: Journal of the National Cancer Institute. - : OXFORD UNIV PRESS INC. - 0027-8874 .- 1460-2105. ; 110:10, s. 1094-1101
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https://academic.oup...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
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- Background: Recent progress in sequencing technologies allows us to explore comprehensive genomic and transcriptomic information to improve the current European LeukemiaNet (ELN) system of acute myeloid leukemia (AML).Methods: We compared the prognostic value of traditional demographic and cytogenetic risk factors, genomic data in the form of somatic aberrations of 25 AML-relevant genes, and whole-transcriptome expression profiling (RNA sequencing) in 267 intensively treated AML patients (Clinseq-AML). Multivariable penalized Cox models (overall survival [OS]) were developed for each data modality (clinical, genomic, transcriptomic), together with an associated prognostic risk score.Results: Of the three data modalities, transcriptomic data provided the best prognostic value, with an integrated area under the curve (iAUC) of a time-dependent receiver operating characteristic (ROC) curve of 0.73. We developed a prognostic risk score (Clinseq-G) from transcriptomic data, which was validated in the independent The Cancer Genome Atlas AML cohort (RNA sequencing, n = 142, iAUC = 0.73, comparing the high-risk group with the low-risk group, hazard ratio [HR] OS = 2.42, 95% confidence interval [CI] = 1.51 to 3.88). Comparison between Clinseq-G and ELN score iAUC estimates indicated strong evidence in favor of the Clinseq-G model (Bayes factor = 26.78). The proposed model remained statistically significant in multivariable analysis including the ELN and other well-known risk factors (HRos = 2.34, 95% CI = 1.30 to 4.22). We further validated the Clinseq-G model in a second independent data set (n = 458, iAUC = 0.66, adjusted HROS = 2.02, 95% CI = 1.33 to 3.08; adjusted HREFS = 2.10, 95% CI = 1.42 to 3.12).Conclusions: Our results indicate that the Clinseq-G prediction model, based on transcriptomic data from RNA sequencing, outperforms traditional clinical parameters and previously reported models based on genomic biomarkers.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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