MicroRNA-181a Shows Promise as a Biomarker for Late-Stage Ovarian Cancer


Key Points

  • Low levels of microRNA-181a expression were associated with better survival outcomes. Higher levels of microRNA-181a expression were found in recurrent ovarian tumors compared with matched primary tumors.
  • MicroRNA-181a regulates epithelial-to-mesenchymal transition and thus, when overexpressed, is associated with an increased tumor burden and a higher incidence of metastases.
  • Stable inhibition of microRNA-181a results in reduced cellular motility and increased survival.

In patients with late-stage epithelial ovarian cancer, high levels of microRNA-181a may be predictive of chemotherapy resistance and disease progression, according to the results of a study reported by Parikh et al in Nature Communications. Thus, microRNA-181a may serve as a biomarker for prognosis and treatment determinations.

Study Details

Numerous clinical pathways exist that may serve as biomarkers for determining outcomes and targeted therapies for epithelial ovarian cancer. A greater understanding of these pathways may lead to improvements in clinical outcomes.

To determine the predictive value of these biomarkers, the investigators analyzed 52 samples of primary human stage III papillary serous ovarian cancers and 23 samples of recurrent stage III/IV tumors from Mount Sinai School of Medicine in New York and San Gerardo Hospital in Monza, Italy. Total real-time RNA (both messenger RNA and microRNA) was analyzed.

Better Outcomes With Low Expression of microRNA-181a

Tumor samples were divided according to expression of high or low levels of microRNA-181a. Tumors with low expression of microRNA-181a were associated with a median progression-free survival rate of 59.9 months, compared with 7.1 months in patients with tumors expressing a high level of microRNA-181a (P = 002). In addition, patients with tumors expressing a low level of microRNA-181a had a median overall survival rate of 66.6 months, compared with 24.9 months in those with tumors expressing a high level of microRNA-181a (P = .002).

Recurrent ovarian tumors were associated with higher levels of microRNA-181a than were primary ovarian tumors. There were no significant differences in the clinical and pathologic characteristics of these two groups.

The investigators expanded their analysis to include microRNA-181b, c, and d. However, only microRNA-181b was readily detectable in all patient samples and, thus, was deemed to be correlated to clinical outcomes. As both microRNA-181a and microRNA-181b are coexpressed from the same cluster and share the same seed region, the investigators concentrated their analysis on microRNA-181a.

Another analysis was conducted targeting the correlation between microRNA-181a expression and epithelial-to-mesenchymal transition, which modulates transforming growth factor-beta (TGF-β) in epithelial ovarian tumors. Expression of microRNA-181a led to epithelial-to-mesenchymal transition. 

Moreover, the investigators found that microRNA-181a is a modulator of TGF-β signaling, which maintains epithelial-to-mesenchymal transition via repression of Smad7. This association between microRNA-181a and TGF-β signaling may play a role in tumor cell survival, effectiveness of chemotherapy, and metastases.

Clinical Implications

Overexpression of microRNA-181a may lead to poor patient outcomes due to the role of microRNA-181a and TGF-β signaling in high-grade ovarian cancer. In addition, from the perspective of the development of future therapies for the management of late-stage ovarian cancer, the discovery that inhibition of microRNA-181a results in a reversion of epithelial-to-mesenchymal transition via decreased TGF-β signaling may lead to improved targeted therapies.   

“This study is one of the first to indicate that it is possible using a novel genomic analysis to identify abnormalities specific to ovarian cancer. Women worldwide will benefit from this discovery,” said Stanton Gerson, MD, Director of the Case Comprehensive Cancer Center and the Seidman Cancer Center at University Hospitals Case Medical Center, in a statement.

Analisa DiFeo, MD, of the Department of Medicine, Case Western Reserve University, Cleveland, is the corresponding author of the article in Nature Communications.

The study was funded by grants from the Ovarian Cancer Research Program CDMRP, Department of Defense, Ovarian Cancer Research Fund Liz Tilberis Scholar, and the Young Scientist Cancer Research Fund at Mount Sinai School of Medicine. The authors disclosed no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.