The 14q32 maternally imprinted locus is a major source of longitudinally stable circulating microRNAs as measured by small RNA sequencing

Understanding the normal temporal variation of serum molecules is a critical factor for identifying useful candidate biomarkers for the diagnosis and prognosis of chronic disease. Using small RNA sequencing in a longitudinal study of 66 women with no history of cancer, we determined the distribution...

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Published inScientific reports Vol. 9; no. 1; pp. 15787 - 12
Main Authors Valbuena, Gabriel N., Apostolidou, Sophia, Roberts, Rhiannon, Barnes, Julie, Alderton, Wendy, Harper, Lauren, Jacobs, Ian, Menon, Usha, Keun, Hector C.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 31.10.2019
Nature Publishing Group
Subjects
38
38/39
45
45/91
631/337/384/331
692/53
Age Factors
Aged
Biomarkers
Biomarkers, Tumor - blood
Biomarkers, Tumor - genetics
Body Mass Index
Centrifugation
Chromosome 14
Chromosomes, Human, Pair 14 - genetics
Chromosomes, Human, Pair 14 - metabolism
Chronic illnesses
Correlation coefficient
Diagnosis
Female
Follow-Up Studies
Genomic Imprinting
Humanities and Social Sciences
Humans
Longitudinal studies
MicroRNAs
MicroRNAs - blood
MicroRNAs - genetics
Middle Aged
miRNA
multidisciplinary
Multigene Family
Ovarian Neoplasms - blood
Ovarian Neoplasms - genetics
RNA, Neoplasm - blood
RNA, Neoplasm - genetics
Science
Science (multidisciplinary)
Sequence Analysis, RNA
Temporal variations
Online AccessGet full text
ISSN2045-2322
2045-2322
DOI10.1038/s41598-019-51948-6

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Abstract Understanding the normal temporal variation of serum molecules is a critical factor for identifying useful candidate biomarkers for the diagnosis and prognosis of chronic disease. Using small RNA sequencing in a longitudinal study of 66 women with no history of cancer, we determined the distribution and dynamics (via intraclass correlation coefficients, ICCs) of the miRNA profile over 3 time points sampled across 2–5 years in the course of the screening trial, UKCTOCS. We were able to define a subset of longitudinally stable miRNAs (ICC >0.75) that were individually discriminating of women who had no cancer over the study period. These miRNAs were dominated by those originating from the C14MC cluster that is subject to maternal imprinting. This assessment was not significantly affected by common confounders such as age, BMI or time to centrifugation nor alternative methods to data normalisation. Our analysis provides important benchmark data supporting the development of miRNA biomarkers for the impact of life-course exposure as well as diagnosis and prognostication of chronic disease.
AbstractList Understanding the normal temporal variation of serum molecules is a critical factor for identifying useful candidate biomarkers for the diagnosis and prognosis of chronic disease. Using small RNA sequencing in a longitudinal study of 66 women with no history of cancer, we determined the distribution and dynamics (via intraclass correlation coefficients, ICCs) of the miRNA profile over 3 time points sampled across 2–5 years in the course of the screening trial, UKCTOCS. We were able to define a subset of longitudinally stable miRNAs (ICC >0.75) that were individually discriminating of women who had no cancer over the study period. These miRNAs were dominated by those originating from the C14MC cluster that is subject to maternal imprinting. This assessment was not significantly affected by common confounders such as age, BMI or time to centrifugation nor alternative methods to data normalisation. Our analysis provides important benchmark data supporting the development of miRNA biomarkers for the impact of life-course exposure as well as diagnosis and prognostication of chronic disease.
Understanding the normal temporal variation of serum molecules is a critical factor for identifying useful candidate biomarkers for the diagnosis and prognosis of chronic disease. Using small RNA sequencing in a longitudinal study of 66 women with no history of cancer, we determined the distribution and dynamics (via intraclass correlation coefficients, ICCs) of the miRNA profile over 3 time points sampled across 2-5 years in the course of the screening trial, UKCTOCS. We were able to define a subset of longitudinally stable miRNAs (ICC >0.75) that were individually discriminating of women who had no cancer over the study period. These miRNAs were dominated by those originating from the C14MC cluster that is subject to maternal imprinting. This assessment was not significantly affected by common confounders such as age, BMI or time to centrifugation nor alternative methods to data normalisation. Our analysis provides important benchmark data supporting the development of miRNA biomarkers for the impact of life-course exposure as well as diagnosis and prognostication of chronic disease.
Understanding the normal temporal variation of serum molecules is a critical factor for identifying useful candidate biomarkers for the diagnosis and prognosis of chronic disease. Using small RNA sequencing in a longitudinal study of 66 women with no history of cancer, we determined the distribution and dynamics (via intraclass correlation coefficients, ICCs) of the miRNA profile over 3 time points sampled across 2-5 years in the course of the screening trial, UKCTOCS. We were able to define a subset of longitudinally stable miRNAs (ICC >0.75) that were individually discriminating of women who had no cancer over the study period. These miRNAs were dominated by those originating from the C14MC cluster that is subject to maternal imprinting. This assessment was not significantly affected by common confounders such as age, BMI or time to centrifugation nor alternative methods to data normalisation. Our analysis provides important benchmark data supporting the development of miRNA biomarkers for the impact of life-course exposure as well as diagnosis and prognostication of chronic disease.Understanding the normal temporal variation of serum molecules is a critical factor for identifying useful candidate biomarkers for the diagnosis and prognosis of chronic disease. Using small RNA sequencing in a longitudinal study of 66 women with no history of cancer, we determined the distribution and dynamics (via intraclass correlation coefficients, ICCs) of the miRNA profile over 3 time points sampled across 2-5 years in the course of the screening trial, UKCTOCS. We were able to define a subset of longitudinally stable miRNAs (ICC >0.75) that were individually discriminating of women who had no cancer over the study period. These miRNAs were dominated by those originating from the C14MC cluster that is subject to maternal imprinting. This assessment was not significantly affected by common confounders such as age, BMI or time to centrifugation nor alternative methods to data normalisation. Our analysis provides important benchmark data supporting the development of miRNA biomarkers for the impact of life-course exposure as well as diagnosis and prognostication of chronic disease.
ArticleNumber 15787
Author Roberts, Rhiannon
Alderton, Wendy
Jacobs, Ian
Barnes, Julie
Menon, Usha
Valbuena, Gabriel N.
Keun, Hector C.
Apostolidou, Sophia
Harper, Lauren
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SubjectTerms 38
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631/337/384/331
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Age Factors
Aged
Biomarkers
Biomarkers, Tumor - blood
Biomarkers, Tumor - genetics
Body Mass Index
Centrifugation
Chromosome 14
Chromosomes, Human, Pair 14 - genetics
Chromosomes, Human, Pair 14 - metabolism
Chronic illnesses
Correlation coefficient
Diagnosis
Female
Follow-Up Studies
Genomic Imprinting
Humanities and Social Sciences
Humans
Longitudinal studies
MicroRNAs
MicroRNAs - blood
MicroRNAs - genetics
Middle Aged
miRNA
multidisciplinary
Multigene Family
Ovarian Neoplasms - blood
Ovarian Neoplasms - genetics
RNA, Neoplasm - blood
RNA, Neoplasm - genetics
Science
Science (multidisciplinary)
Sequence Analysis, RNA
Temporal variations
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Title The 14q32 maternally imprinted locus is a major source of longitudinally stable circulating microRNAs as measured by small RNA sequencing
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