microRNAs as Prognostic Biomarkers in Malignant Melanoma
Marie S Abi Daoud, Paulo Nuin, Jiamen Chen, Xiao Zhang, Harriet Feilloter, Victor A Tron. Queen's University, Kingston, ON, Canada
Background: MicroRNAs (miRs) are important regulatory molecules. Many recent advances have shown their dysregulation in cancer. Our laboratory has previously reported altered expression of key miRs in melanoma. To develop a further understanding of the clinical importance of such miRs, we have assembled a cohort of primary melanoma patients.
Design: The Agilent miRNA microarray platform was used to generate global miRNA expression profiles for 66 primary melanoma tissue samples. The tumours were from single institution cases, with uniform treatment and follow-up protocols for which clinical data were available. Using supervised analyses, we looked for association of expression level for each miR with pathological (Breslow depth less than or equal to 2mm versus greater than 2mm and low mitotic count versus high mitotic count) and clinical (no metastatic progression versus presence of distant or regional metastasis and alive versus deceased) endpoints.
Results: We identified numerous miRs whose expression level appeared associated with both clinical and pathological endpoints, in most cases showing lowered expression in the more aggressive disease. Of particular interest, we found that expression of miR-150 as well as members of the miR-200 family were significantly associated with the pathological endpoints measured. These miRs were relatively downregulated in thicker melanomas and those with high mitotic rates compared to the thinner or less mitotically active tumours. When clinical endpoints were assessed, lower expression of miR-150 was also strikingly correlated with death and with the presence of metastatic disease.
Conclusions: We conclude that miR expression levels measured in the primary diagnostic lesion can be used to prognosticate clinical outcome in melanoma. The miR-200 family and miR-150 appear to be most promising in this regard. We are currently investigating a role for these miRs and their putative target mRNAs in melanoma progression and outcome, using experimental, statistical and bioinformatics approaches.
Monday, March 19, 2012 11:45 AM
Platform Session: Section F, Monday Morning