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Serum RNAs can predict lung cancer up to 10 years prior to diagnosis

Lung cancer (LC) prognosis is closely linked to the stage of disease when diagnosed. We investigated the biomarker potential of serum RNAs for the early detection of LC in smokers at different prediagnostic time intervals and histological subtypes. In total, 1061 samples from 925 individuals were an...

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Autores principales: Umu, Sinan U, Langseth, Hilde, Zuber, Verena, Helland, Åslaug, Lyle, Robert, Rounge, Trine B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8884722/
https://www.ncbi.nlm.nih.gov/pubmed/35147498
http://dx.doi.org/10.7554/eLife.71035
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author Umu, Sinan U
Langseth, Hilde
Zuber, Verena
Helland, Åslaug
Lyle, Robert
Rounge, Trine B
author_facet Umu, Sinan U
Langseth, Hilde
Zuber, Verena
Helland, Åslaug
Lyle, Robert
Rounge, Trine B
author_sort Umu, Sinan U
collection PubMed
description Lung cancer (LC) prognosis is closely linked to the stage of disease when diagnosed. We investigated the biomarker potential of serum RNAs for the early detection of LC in smokers at different prediagnostic time intervals and histological subtypes. In total, 1061 samples from 925 individuals were analyzed. RNA sequencing with an average of 18 million reads per sample was performed. We generated machine learning models using normalized serum RNA levels and found that smokers later diagnosed with LC in 10 years can be robustly separated from healthy controls regardless of histology with an average area under the ROC curve (AUC) of 0.76 (95% CI, 0.68–0.83). Furthermore, the strongest models that took both time to diagnosis and histology into account successfully predicted non-small cell LC (NSCLC) between 6 and 8 years, with an AUC of 0.82 (95% CI, 0.76–0.88), and SCLC between 2 and 5 years, with an AUC of 0.89 (95% CI, 0.77–1.0), before diagnosis. The most important separators were microRNAs, miscellaneous RNAs, isomiRs, and tRNA-derived fragments. We have shown that LC can be detected years before diagnosis and manifestation of disease symptoms independently of histological subtype. However, the highest AUCs were achieved for specific subtypes and time intervals before diagnosis. The collection of models may therefore also predict the severity of cancer development and its histology. Our study demonstrates that serum RNAs can be promising prediagnostic biomarkers in an LC screening setting, from early detection to risk assessment.
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spelling pubmed-88847222022-03-01 Serum RNAs can predict lung cancer up to 10 years prior to diagnosis Umu, Sinan U Langseth, Hilde Zuber, Verena Helland, Åslaug Lyle, Robert Rounge, Trine B eLife Cancer Biology Lung cancer (LC) prognosis is closely linked to the stage of disease when diagnosed. We investigated the biomarker potential of serum RNAs for the early detection of LC in smokers at different prediagnostic time intervals and histological subtypes. In total, 1061 samples from 925 individuals were analyzed. RNA sequencing with an average of 18 million reads per sample was performed. We generated machine learning models using normalized serum RNA levels and found that smokers later diagnosed with LC in 10 years can be robustly separated from healthy controls regardless of histology with an average area under the ROC curve (AUC) of 0.76 (95% CI, 0.68–0.83). Furthermore, the strongest models that took both time to diagnosis and histology into account successfully predicted non-small cell LC (NSCLC) between 6 and 8 years, with an AUC of 0.82 (95% CI, 0.76–0.88), and SCLC between 2 and 5 years, with an AUC of 0.89 (95% CI, 0.77–1.0), before diagnosis. The most important separators were microRNAs, miscellaneous RNAs, isomiRs, and tRNA-derived fragments. We have shown that LC can be detected years before diagnosis and manifestation of disease symptoms independently of histological subtype. However, the highest AUCs were achieved for specific subtypes and time intervals before diagnosis. The collection of models may therefore also predict the severity of cancer development and its histology. Our study demonstrates that serum RNAs can be promising prediagnostic biomarkers in an LC screening setting, from early detection to risk assessment. eLife Sciences Publications, Ltd 2022-02-11 /pmc/articles/PMC8884722/ /pubmed/35147498 http://dx.doi.org/10.7554/eLife.71035 Text en © 2022, Umu et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Umu, Sinan U
Langseth, Hilde
Zuber, Verena
Helland, Åslaug
Lyle, Robert
Rounge, Trine B
Serum RNAs can predict lung cancer up to 10 years prior to diagnosis
title Serum RNAs can predict lung cancer up to 10 years prior to diagnosis
title_full Serum RNAs can predict lung cancer up to 10 years prior to diagnosis
title_fullStr Serum RNAs can predict lung cancer up to 10 years prior to diagnosis
title_full_unstemmed Serum RNAs can predict lung cancer up to 10 years prior to diagnosis
title_short Serum RNAs can predict lung cancer up to 10 years prior to diagnosis
title_sort serum rnas can predict lung cancer up to 10 years prior to diagnosis
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8884722/
https://www.ncbi.nlm.nih.gov/pubmed/35147498
http://dx.doi.org/10.7554/eLife.71035
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