Comparison of the Metastasis Predictive Potential of mRNA and Long Non-Coding RNA Profiling in Systemically Untreated Breast Cancer

Thi T.N. Do, Ines Block, Mark Burton, Kristina P. Sørensen, Martin J. Larsen, Martin Bak, Søren Cold, Mads Thomassen, Qihua Tan, Torben A. Kruse*

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Abstrakt

Several gene expression signatures based on mRNAs and a few based on long non-coding RNAs (lncRNAs) have been developed to provide prognostic information beyond clinical evaluation in breast cancer (BC). However, the comparison of such signatures for predicting recurrence is very scarce. Therefore, we compared the prognostic utility of mRNAs and lncRNAs in low-risk BC patients using two different classification strategies. Frozen primary tumor samples from 160 lymph node negative and systemically untreated BC patients were included; 80 developed recurrence—i.e., regional or distant metastasis while 80 remained recurrence-free (mean follow-up of 20.9 years). Patients were pairwise matched for clinicopathological characteristics. Classification based on differential mRNA or lncRNA expression using seven individual machine learning methods and a voting scheme classified patients into risk-subgroups. Classification by the seven methods with a fixed sensitivity of ≥90% resulted in specificities ranging from 16–40% for mRNA and 38–58% for lncRNA, and after voting, specificities of 38% and 60% respectively. Classifier performance based on an alternative classification approach of balanced accuracy optimization also provided higher specificities for lncRNA than mRNA at comparable sensitivities. Thus, our results suggested that classification followed by voting improved prognostic power using lncRNAs compared to mRNAs regardless of classification strategy.
OriginalsprogEngelsk
Artikelnummer4907
TidsskriftCancers
Vol/bind13
Udgave nummer19
ISSN2072-6694
DOI
StatusUdgivet - 1. okt. 2021

Bibliografisk note

Funding Information:
Funding: This research was funded by the Danish Cancer Society, the Danish Council for Independent Research (grants: 7016-00346B/FSS and 09-061677/FSS), the Danish Ministry of the Interior, the University of Southern Denmark (Horizon2020, grant: DAWN2020), the Danish Council for Strategic Research (grant: DBCG-TIBCAT) and Regionernes Medicinpulje, Dansk Kræft-forskningsfond, Breast Friends, Fonden til Lægevidenskabens Fremme, Meta & Håkon Baggers Fond, A. J. Andersen & hustrus Fond, Inge & Jørgen Larsens Mindelegat, Overlægerådets Legatudvalg, Direktør Jacob Madsens & Hustru Olga Madsens Fond, Fru Ingeborg Anna Albinus Larsens Mindelegat, Fonden af 1870, Harboefonden, the Odense University Hospital Fund for Free Research, Lundbeckfonden (grant: Center of Excellence NanoCAN), and Frimodt-Heineke Fonden.

Funding Information:
This research was funded by the Danish Cancer Society, the Danish Council for Independent Research (grants: 7016-00346B/FSS and 09-061677/FSS), the Danish Ministry of the Interior, the University of Southern Denmark (Horizon 2020, grant: DAWN2020), the Danish Council for Strategic Research (grant: DBCG-TIBCAT) and Regionernes Medicinpulje, Dansk Kr?ft-forskningsfond, Breast Friends, Fonden til L?gevidenskabens Fremme, Meta & H?kon Baggers Fond, A. J. Andersen & hustrus Fond, Inge & J?rgen Larsens Mindelegat, Overl?ger?dets Legatudvalg, Direkt?r Jacob Madsens & Hustru Olga Madsens Fond, Fru Ingeborg Anna Albinus Larsens Mindelegat, Fonden af 1870, Harboefonden, the Odense University Hospital Fund for Free Research, Lundbeckfonden (grant: Center of Excellence NanoCAN), and Frimodt-Heineke Fonden.

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