Dataset Information

Exploration of genome-wide circulating microRNA in hepatocellular carcinoma: MiR-483-5p as a potential biomarker.

ABSTRACT: MicroRNAs (miRNA) are abundant in the circulation and play a central role in diverse biologic processes; they may be useful for early diagnosis of hepatocellular carcinoma.We conducted a two-phase, case-control study (20 pairs for the discovery set and 49 pairs for the validation set) to test the hypothesis that genome-wide dysregulation of circulating miRNAs differentiates hepatocellular carcinoma cases from controls. Taqman low-density arrays were used to examine genome-wide miRNA expression for the discovery set, and quantitative real-time PCR was used to validate candidate miRNAs for both discovery and validation sets.Sixty-six miRNAs were found to be significantly overexpressed in plasma of hepatocellular carcinoma cases compared with controls after adjusting for false discovery rate (P < 0.05). A volcano plot indicated that seven miRNAs had greater than 2-fold case-control differences with P < 0.01. Four significant miRNAs (miR-150, miR-30c, miR-483-5p, and miR-520b) detectable in all samples with varied expression levels were further validated in a validation set. MiR-483-5p was statistically significantly overexpressed in hepatocellular carcinoma cases compared with controls (3.20 vs. 0.82, P < 0.0001). Hepatocellular carcinoma risk factors and clinic-pathological characteristics did not influence miR-483-5p expression. The combination of plasma miR-483-5p level and hepatitis C virus status can significantly differentiate hepatocellular carcinoma cases from controls with an area under the curve of 0.908 (P < 0.0001). The sensitivity and specificity were, respectively, 75.5% and 89.8%.These preliminary results suggest the importance of dysregulated circulating miR-483-5p as a potential hepatocellular carcinoma biomarker.Confirmation of aberrant expression of miR-483-5p in a large prospective hepatocellular carcinoma study will provide support for its application to hepatocellular carcinoma detection.

SUBMITTER: Shen J

PROVIDER: S-EPMC3963823 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exploration of genome-wide circulating microRNA in hepatocellular carcinoma: MiR-483-5p as a potential biomarker.

Shen Jing J Wang Antai A Wang Qiao Q Gurvich Irina I Siegel Abby B AB Remotti Helen H Santella Regina M RM

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20131014 12

<h4>Background</h4>MicroRNAs (miRNA) are abundant in the circulation and play a central role in diverse biologic processes; they may be useful for early diagnosis of hepatocellular carcinoma.<h4>Methods</h4>We conducted a two-phase, case-control study (20 pairs for the discovery set and 49 pairs for the validation set) to test the hypothesis that genome-wide dysregulation of circulating miRNAs differentiates hepatocellular carcinoma cases from controls. Taqman low-density arrays were used to exa ...[more]

PMID: 24127413

Similar Datasets

Project description:Novel biomarkers for personalizing anticoagulation remain undetermined. We aimed to investigate the association of plasma miRNAs with pharmacokinetic-pharmacodynamic (PK-PD) profiles of rivaroxaban. This is a multicenter, exploratory study of miRNAs in a Chinese population. Healthy volunteers and patients receiving rivaroxaban were enrolled in the study. The area under the plasma concentration-time curve from time 0-t h (AUC0-t) and anti-Xa activity at 3 h (AXA3h) were measured in healthy volunteers, and AXA3h was measured in patients. MiRNAs were detected by miRNA microarray in 26 healthy volunteers with 20 mg rivaroxaban, and quantitative reverse transcription polymerase chain reaction was used to exclude undetectable ones. MiR-320a-3p and miR-483-5p were then quantified in 65 healthy volunteers and 71 patients. MiRNA levels at 3 h were compared between high and low AXA3h or AUC0-t subjects and in matched patients with or without bleeding during follow-up. The miRNA targets were predicted by TargetScan, miRTarBase, and miRDB. Validated genes were included in GO enrichment and KEGG analyses. The protein-protein interaction network was established by STRING and visualized by Cytoscape. A total of 136 Chinese subjects completed the study. In healthy volunteers taking 15 mg rivaroxaban, the miR-320a level at 3 h was significantly positively correlated with AXA3h and AUC0-t (r = 0.359, p = 0.025; r = 0.370, p = 0.02, respectively). A positive correlation was also observed between miR-483 and AXA3h or AUC0-t (r = 0.372, p = 0.02; r = 0.523, p = 0.001, respectively). MiR-320a and miR-483 levels at 3 h in the higher AUC0-t group were significantly higher than those at 0 h. MiR-483 levels at 3 h may distinguish healthy volunteers with high or low AXA3h or AUC0-t. In the 10 mg fed subgroup, higher 3 h mir-483 levels were also observed compared with the control group. No significant differences were found in the comparisons among patients. Bioinformatic analysis showed that these miRNAs may play a regulatory role by targeting ABCG2, ITGB3, PTEN, MAPK1/3, etc. CONCLUSIONS: MiR-320a and miR-483 levels were found to be associated with PK and PD profiles of rivaroxaban in healthy Chinese subjects. Further studies are required to verify these findings and explore the mechanisms.

Dataset Information

Exploration of genome-wide circulating microRNA in hepatocellular carcinoma: MiR-483-5p as a potential biomarker.

Publications

Exploration of genome-wide circulating microRNA in hepatocellular carcinoma: MiR-483-5p as a potential biomarker.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets