Poster Presentation 29th Lorne Cancer Conference 2017

Phase 2 study of circulating microRNA biomarkers in metastatic prostate cancer (#205)

Hui-Ming Lin 1 , Kate L Mahon 1 2 , Calan Spielman 1 , Howard Gurney 3 , Girish Mallesara 4 , Martin R Stockler 2 5 , Patricia Bastick 6 , Karen Briscoe 7 , Gavin Marx 8 , Alex Swarbrick 1 , Lisa G Horvath 1 2
  1. Cancer Research Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. Chris O'Brien Lifehouse, Royal Prince Alfred Hospital, Camperdown, NSW, Australia
  3. Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia
  4. Calvary Mater Newcastle Hospital, Waratah, NSW, Australia
  5. Concord Repatriation General Hospital, Concord, New South Wales, Australia
  6. St George Hospital, Kogarah, New South Wales, Australia
  7. Mid North Coast Cancer Institute, Coffs Harbour Health Campus, Coffs Harbour, New South Wales, Australia
  8. Sydney Adeventist Hospital, Wahroonga, New South Wales, Australia

Background

Biomarkers of therapeutic response and prognosis are needed to assist in the sequencing of treatments for metastatic castration-resistant prostate cancer (CRPC). MicroRNAs are regulators of gene expression, and are shown to be involved in tumour progression. Previously in a Phase 1 discovery study of 97 patients with CRPC, we identified 14 circulating microRNAs that were associated with response to docetaxel chemotherapy or overall survival. We performed a Phase 2 validation study to verify these findings.

Methods

Using real-time PCR and Taqman assays, the levels of the 14 microRNAs were measured in plasma collected before and after the first cycle of docetaxel from a Phase 2 cohort of 89 patients with CRPC.

Results

None of the microRNAs were associated with docetaxel response in the Phase 2 cohort. Higher baseline levels of six microRNAs, predominantly of the miR-200 family, were confirmed to be associated with shorter overall survival. A microRNA signature comprising these six microRNAs predicted high risk patients in the Phase 2 cohort with a hazard ratio of 4.12 (95% CI 2.20-7.70, P = 0.000001). The signature was an independent predictor (P = 0.001) in multivariable analysis with clinicopathological factors (hemoglobin P = 0.06; alkaline phosphatase P = 0.85; serum prostate serum antigen, P = 0.60) in the Phase 2 cohort.

Conclusions

The association of the six microRNAs with prognosis suggests their involvement in CRPC pathogenesis. Further research is required to determine if these microRNAs could be targeted with microRNA-based therapeutics to improve patient outcome.