The miR-200 family controls beta-tubulin III expression and is associated with paclitaxel-based treatment response and progression-free survival in ovarian cancer patients

Endocr Relat Cancer. 2010 Dec 21;18(1):85-95. doi: 10.1677/ERC-10-0148. Print 2011 Feb.

Abstract

Ovarian cancer remains one of the leading causes of cancer deaths. Thus, new biomarkers predictive of response to the standard paclitaxel-carboplatin treatment are needed to improve chemotherapy strategies. MicroRNAs have the potential to modify drug outcomes. Based on this, we have demonstrated in this study that patients with a high expression of the miR-200 family show low levels of β-tubulin class III in ovarian carcinoma. In addition, we have established the clinical relevance of these microRNAs for ovarian cancer patients' treatment response and survival. In a well-characterized series of 72 ovarian carcinomas, the expressions of miR-141, miR-200a, miR-200b, miR-200c, and miR-429 were quantified by quantitative reverse transcription-PCR, and the protein content of β-tubulin isotypes I, II, and III was determined by immunohistochemistry. The relationship between these microRNAs, β-tubulin expression, response to paclitaxel-based treatment, progression-free survival (PFS) and overall survival was determined. While isotype I had constant high levels, protein expression of β-tubulins II and III was mutually exclusive. Low tumoral miR-200 expression was significantly associated with high β-tubulin III protein content (P values range, 0.047-<0.0001), and patients without complete response (CR) had lower miR-200c levels than patients with CR (hazard ratio (HR)=1.43, 95% confidence interval (CI)=1.02-1.99, P=0.037, multivariate analysis). Additionally, low miR-200 family expression had a trend toward poor PFS (HR>2.0, P values 0.051, 0.054, and 0.079 for miR-200c, miR-141, and miR-429 respectively, multivariate analysis). In conclusion, miR-200 family members affect the final β-tubulin III protein content of ovarian carcinomas. Furthermore, these microRNAs might constitute the biomarkers of response to paclitaxel-based treatments and relapse/progression of advanced stage ovarian carcinoma patients.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Pharmacological / analysis
  • Biomarkers, Pharmacological / metabolism
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma / diagnosis
  • Carcinoma / drug therapy*
  • Carcinoma / genetics
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / analysis
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Middle Aged
  • Multigene Family / genetics
  • Multigene Family / physiology
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Paclitaxel / administration & dosage*
  • Prognosis
  • Retrospective Studies
  • Tubulin / genetics*
  • Tubulin / metabolism

Substances

  • Biomarkers, Pharmacological
  • Biomarkers, Tumor
  • MIRN200 microRNA, human
  • MicroRNAs
  • Tubulin
  • Paclitaxel