Analysis of serum genome-wide microRNAs for breast cancer detection

Clin Chim Acta. 2012 Jul 11;413(13-14):1058-65. doi: 10.1016/j.cca.2012.02.016. Epub 2012 Feb 23.


Objective: Among methods for profiling levels of miRNAs, next-generation sequencing (NGS) has an effective one for genome-wide profiles, which not only can accurately quantify known miRNAs expression, but also discovery novel miRNAs. In this paper, we investigated that whether specific miRNAs were co-expressed in the serum and tissue of breast cancer (BC) patients as novel biomarkers by SOLiD sequencing.

Methods: Different miRNA expression profiles of serum and tissue in breast cancer patients and control subjects were obtained by NGS -SOLiD sequencing. Real-time PCR was used to selected and validated candidate miRNA-biomarkers. Novel miRNAs were predicted by computational pipeline, and validated by Northern blot analysis.

Results: Of genome-wide miRNA analysis using SOLiD sequencing, 7 miRNAs were found to be co-upregulated (i.e., miR-103, miR-23a, miR-29a, miR-222, miR-23b, miR-24 and miR-25). miR-222 was significantly increased in the serum of BC patients by further validation(P<0.05), which may be a useful biomarker for differentiating BC patients from controls with receiver operating characteristic (ROC) curve area 0.67 of (95% CI=0.5649 to 0.7775). A novel miRNA, named miR-BS1 was preliminarily identified and validated. Pre-miR-BS1 has a characteristic secondary structure. Mature miR-BS1 expression was detected in MCF-7 and MDA-MB-231 cells. Through gene ontology analysis, predicted target genes of miR-BS1, such as FOXO3 and KRAS, were involved in cancer-related signaling pathway.

Conclusions: This study presented a connection between serum- and tissue- based miRNA of breast cancer which suggested that serum-miRNAs may be potential biomarkers for BC detection. And next-generation sequencing will provide a robust platform for miRNA profilings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / blood*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Cell Line, Tumor
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic / genetics*
  • Genome-Wide Association Study*
  • Humans
  • MicroRNAs / blood*
  • MicroRNAs / genetics*
  • Middle Aged
  • ROC Curve


  • MicroRNAs