Serum microRNA-195 is down-regulated in breast cancer: a potential marker for the diagnosis of breast cancer

Mol Biol Rep. 2014 Sep;41(9):5913-22. doi: 10.1007/s11033-014-3466-1. Epub 2014 Aug 8.

Abstract

MicroRNA-195 (miR-195) is a tumor suppressor that plays an important role in tumorigenesis. There are few studies on miR-195 expression in breast cancer patients and the results have been inconsistent; therefore, this study examined miR-195 expression in the serum of BC patients. Samples from 102 normal subjects and 210 subjects with BC who had detailed clinical follow-up information available were selected. An internal reference (miR-16) and serum miR-195 were amplified and quantitatively detected by SYBR green-based real-time RT-PCR. We analyzed the differences in miR-195 levels between BC and healthy cases and the relationships between the miR-195 level and TNM stage and other clinicopathological parameters. In addition, changes in miR-195 levels were examined for 21 BC cases using paired samples before and after neoadjuvant chemotherapy. miR-195 was downregulated in BC compared with control samples (P = 0.000, Mann-Whitney U test). The sensitivity and specificity of miR-195 in the diagnosis of BC were 69.0 and 89.2 %, respectively; whereas, the sensitivities of carcinoembryonic antigen (CEA) and carbohydrate antigen 153 (CA153) were only 15.08 and 21.1 %, respectively. Remarkably, serum miR-195 had higher sensitivity, 73.97 % (108/146), as a tumor marker in the diagnosis of early stage BC [ductal carcinoma in situ, tumor-node-metastasis (TNM) I, II] compared with the conventional tumor markers CA153 and CEA (12.41 and 7.59 %). Moreover, compared with CEA and CA153, miR-195 had a higher sensitivity for detecting the response to neoadjuvant chemotherapy and significantly increased, more than twofold, after neoadjuvant chemotherapy (P = 0.025, paired t test) in 52.381 % (11/21) of BC cases. However, there were no significant relationships between miR-195 expression and other clinicopathological parameters (TNM stage/pathotype/ER/PR/lymph node status). Our data indicate serum miR-195 is a promising tumor marker for BC diagnosis and general screening, especially for early stage BC. The high sensitivity of miR-195 to neoadjuvant chemotherapy may lay the foundation for future studies on the use of miRNA-based methods for monitoring BC treatment and therapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Tumor-Associated, Carbohydrate / blood
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / therapy
  • Carcinoembryonic Antigen / blood
  • Case-Control Studies
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genetic Markers*
  • Humans
  • Lymphatic Metastasis
  • MicroRNAs / blood*
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoadjuvant Therapy
  • Reproducibility of Results
  • Sensitivity and Specificity

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Carcinoembryonic Antigen
  • Genetic Markers
  • MIRN195 microRNA, human
  • MicroRNAs