Intra-individual variation of miRNA expression levels in human plasma samples

Abstract

Background: Circulating miRNAs as potential non-invasive biomarkers for disease risk assessment and cancer early diagnosis have attracted increasing interest. Little information, however, is available regarding the intra-individual variation of circulating miRNA levels.

Methods: We measured expression levels of a panel of 800 miRNAs in repeated plasma samples from 51 healthy individuals that were collected 6 to 12 months apart and evaluated the intra-individual variation by the intra-class correlation coefficient (ICC).

Results: After background correction, a total of 185 miRNAs were detected in at least 10% of the plasma samples, with 69 and 28 miRNAs being detected in 50% and 90% of samples, respectively. The median ICC was 0.46 for these 185 miRNAs. Among them, 41% (75 miRNAs) had an ICC ≥ 0.5, and 23% (42 miRNAs) had an ICC ≥ 0.6. The ICC is higher for miRNAs with higher expression levels or higher detection rates, when compared to those with lower expression levels or lower detection rates.

Conclusions: These results suggest that common circulating miRNAs are stable over a relatively long period and can serve as reliable biomarkers for epidemiological and clinical research.

Keywords:

• Circulating miRNA
• intra-individual variation
• intra-class correlation coefficient
• biomarkers
• epidemiology

Acknowledgments

The authors wish to thank the study participants and research staff for their contributions and commitment to this project. We thank Regina Courtney for laboratory assistance and Nan Kennedy for assistance with editing and manuscript preparation. The sample preparation was performed at the Survey and Biospecimen Shared Resource, which is supported in part by the Vanderbilt-Ingram Cancer Center (P30CA068485).

Disclosure statement

The authors report no declarations of interest.

Additional information

Funding

This study is supported by UM1 CA182910 (to W. Zheng), UM1 CA173640 and NO2-CP11010-66 (to X.-O. Shu), and by the Vanderbilt-Ingram Cancer Center Professorship fund.