Abstract 4285: Intra-individual variation in circulating miRNA expression levels in human plasma samples

Abstract

Abstract Circulating miRNAs as possible non-invasive biomarkers for disease risk assessment and cancer early diagnosis has attracted increasing interest. Little information, however, is available regarding the intra-individual variation of circulating miRNA levels. We measured miRNA expression in repeated plasma samples that were collected 6 to 12 months apart from 53 healthy individuals participating in a sub-study nested in the Shanghai Women's and Shanghai Men's Health Studies. Total RNA, including miRNA, was isolated from plasma using Qiagen's miRNeasy Serum/Plasma Kit. Three synthetic spike-in RNA oligos (osa-miR414, cel-miR248, and ath-miR159a) were added to control for variances in the starting material and the efficiency of RNA extraction. NanoString's Human v2 miRNA Expression Assay, which includes CodeSets of probes specific for 800 common human miRNAs, was used for the miRNA assays. The derived miRNA counts were first corrected by subtracting the background counts and then were normalized by using the average count from three spike-in oligos and the top fifty miRNAs that gave most significant hybridization signals. The intra-individual variation was evaluated by an intra-class correlation coefficient (ICC). A total of 185 miRNAs were detected in at least 10% of samples. The detectable rate varied for each miRNA, with 69 and 44 miRNAs being detected in 50% and 75% of samples, respectively. The median ICC was 0.46 for all of the 185 detectable miRNAs. Among them, 41% (75 miRNAs) had an ICC ≥0.5, and 42 miRNAs had an ICC ≥0.6. The ICC is higher for miRNAs with higher expression levels and higher detection rates, when compared to their counterparts with lower expression or detection rates. In summary, we found that 185 miRNAs were expressed in at least 10% of plasma samples, and 69 miRNAs in 50% of samples from healthy Chinese men and women, and that 75 of these miRNAs had an ICC ≥0.5. These results suggest that common circulating miRNAs can serve as reliable biomarkers for epidemiological and clinical research. Citation Format: Jie Wu, Hui Cai, Yong-Bing Xiang, Charles Matthews, Fei Ye, Wei Zheng, Qiuyin Cai, Xiao-Ou Shu. Intra-individual variation in circulating miRNA expression levels in human plasma samples. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4285.