Going macro from micro – harnessing the power of serum microRNAs to predict surgical outcome for women with ovarian cancer (14245)
Background
Optimal cytoreduction, complete
surgical removal of the tumour, is one of the most important prognostic factors
for women with ovarian cancer, yet remains challenging to predict prior to
surgery. A molecular tool to assist in this prediction, in combination with
other clinical factors, could help plan surgery and decide the best treatment
options for individual patients. Short RNAs called microRNAs circulating in the
blood are promising biomarkers due to their stability and disease-specific
expression. However, interference from microRNAs released from erythrocytes
poses a significant issue for the biomarker discovery process.
Aims:
1) To test the sensitivity of existing methods to identify
haemolysed serum samples.
2) To identify a panel of microRNAs that could separate women
with ovarian cancer from healthy women and further, to predict their surgical
outcome.
Methods:
Healthy volunteer blood was haemolysed by sonication and serially diluted to
obtain standards to be measured by a number of methods. Pre-surgical sera of
fifteen and thirteen ovarian cancer patients with optimal cytoreduction and
suboptimal cytoreduction, respectively, and fifteen age-matched healthy women
were sourced from the Kolling Institute’s Tumour bank. Expression of 167 microRNAs
was measured using Serum/Plasma focus panel (Exiqon, # 203843). Data were
analysed using GenEx software (v 6.0, Exiqon).
Results and conclusions:
Samples predicted to have less than 0.25% haemolysis by spectrophotometric
analysis, which could detect ≥ 0.0625% haemolysis, were used for microRNA
profiling. Preliminary analysis identified sixteen differentially expressed
microRNAs across the three test groups, including miR-210 known to be elevated
in ovarian cancer and an important regulator of the hypoxic response.
Additionally, microRNAs stably expressed across all three groups were
identified and may have value for normalisation. Candidate
microRNAs are currently being validated in an independent cohort, data from
which will be pooled with the serum glycoprotein biomarker CA-125 to assess for
improved predictive power.