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Prostate Cancer Recurrence Signatures Proposed From MicroRNA Meta-Analysis

NEW YORK (GenomeWeb) – A new study suggests that it may be feasible to use differentially expressed microRNAs as a window for predicting prostate cancer recurrence in individuals treated with radical prostatectomy surgery.

Researchers from Turkey, Iran, and the US did a meta-analysis of array-based miRNA profiles detected post-surgically in men with prostate cancer based on half a dozen existing datasets from five prior studies. The findings, appearing online today in PLOS One, support the notion that there is a miRNA signature comprised of 37 miRNAs that are consistently enhanced or dialed down in individuals who go on to develop cancer recurrence after radical prostatectomy surgery.

With these miRNAs, the team used network, pathway, and other analyses to explore the gene expression shifts and target genes related to the recurrence signature, highlighting epithelial cell proliferation, tissue morphogenesis, and cancer-related pathways. The group also established an 11-miRNA classifier for predicting biochemical prostate cancer recurrence, which appeared to have up to 97 percent accuracy.

"[I]t was shown that the combination of [differentially expressed] miRNAs can assist in the more specific detection of [prostate cancer] and prediction of biochemical recurrence," senior author Nizamettin Aydin, a computer engineering researcher at the Yildiz Technical University in Istanbul, and his co-authors wrote.

Despite the availability of radiation, hormone treatment, and prostatectomy treatments, the team explained, there is still a need to boost overall survival rates in prostate cancer. And that has prompted interest in predicting biochemical recurrence — marked by elevated prostate-specific antigen levels in the blood — for the almost one-third of men treated for prostate cancer.

For their analysis, the researchers used a method called MetaDE to evaluate array-based miRNA profiles in more than 300 tumor samples from individuals with or without biochemical disease recurrence after prostate cancer treatment, searching for miRNAs with significant differential expression in the recurrence cases. In the process, they found 15 miRNAs with enhanced recurrence-associated expression in two or more datasets and another 22 miRNAs with muted expression in the recurrence cases.

By bringing in target gene clues, gene ontology information, network profiles, gene set enrichment analyses, and more, the team began delineating the pathways and processes that appeared to be altered in individuals on the path to prostate cancer recurrence.

And from the initial 37-miRNA set, the researchers narrowed in on miRNA classifiers showing the most promise as predictive biochemical recurrence markers in each dataset. For example, they reported that an 11-miRNA signature successfully distinguished prostate cancer cases with or without biochemical recurrence with 97 percent accuracy in 40 prostate cancer cases originally profiled with an Agilent array.

The authors noted that all but one of the miRNAs that were associated with biochemical recurrence of prostate cancer in the meta-analysis have been implicated in prostate cancer and/or other cancer types in the past.

"The identified genes have been known as tumor suppressors and biomarkers which are closely related to several cancer types, such as colorectal cancer, breast cancer, [prostate cancer], gastric, and hepatocellular carcinomas," they wrote.