Poster Presentation 28th Lorne Cancer Conference 2016

Differentially expressed microRNAs in circulating leucocytes from patients with locally advanced rectal cancer (#157)

Benjamin H.L Harris 1 2 3 , Stephanie H Lim 1 3 4 , Paul De Souza 1 4 5 , Wei Chua 1 4 , Weng Ng 1 4 , Mark Cowley 6 , Kevin J Spring 1 3 5
  1. Ingham Institute, Sydney, Liverpool, NSW, Australia
  2. St.Anne’s College, University of Oxford, Oxford, UK
  3. South-western Sydney Clinical School, University of New South Wales, Liverpool, Sydney, Australia
  4. Cancer Therapy Centre, Liverpool Hospital, Liverpool, , Sydney, Australia
  5. Western Sydney University, Liverpool, Sydney, NSW, Australia
  6. Kinghorn Centre for Clinical Genomics, Garvan Institute, Darlinghurst, Sydney, NSW, Australia

The impact of molecular alterations associated with tumorigenesis may be reflected within the circulating leucocyte population of peripheral blood. There is little known about the microRNA expression profile of leucocytes from patients with rectal cancer. In this study we investigated microRNA (miRNA) expression in circulating leucocytes in patients with locally advanced rectal cancer (LARC).

 

Twenty-one patients with LARC were recruited as part of this study and blood samples were collected from all patients pre-commencement of neoadjuvant chemoradiation. Circulating tumour cells were then enumerated using the IsofluxTM system (Fluxion Biosciences Inc.). A Taqman OpenArray panel of 112 miRNAs was analysed using the QuantStudioTM 12K Flex platform and expression data was normalised to the endogenous control (U6 snRNA). Differences in expression were established using the ∆∆Ct method. Patients with “normal” CTC number (<2) were identified and the leucocyte miRNA expression profile was compared to healthy controls. This threshold was determined after analysis of CTC numbers from 10 healthy controls. Differentially expressed miRNAs were identified and their expression compared to the same panel of miRNAs in patients with high numbers of CTCs (>10). Bioinformatic analysis was performed using R. Mean expressions were compared using a student’s t-test.

 

Six miRNAs appeared to be significantly differentially expressed in leucocytes of LARC patients: let-7b, let-7e, miR-10b*, miR-222, miR-483-5p and miR-630 (p<0.05). All were expressed significantly lower in LARC patients, with miR-630 appearing particularly downregulated, by approximately six-fold.

Further work is being conducted to understand the functional implications of the apparent downregulation of miR-630 in this context.