A new study led by researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) revealed that a specific group of molecules expressed in prostate cancer cells can predict cancer recurrence and the response to radiation therapy in patients who have undergone prostate removal. The study was published in the journal PLOS ONE and is entitled “A Novel MiRNA-Based Predictive Model for Biochemical Failure Following Post-Prostatectomy Salvage Radiation Therapy.”
Prostate cancer is the second most common cancer in men, with almost one million new cases diagnosed every year worldwide. In the United States, 220,800 new cases will be diagnosed in 2015. Prostate cancer is a curable cancer that can range from slow-growing tumors (more common) to rapidly progressing aggressive tumors and its diagnosis can be made through the analysis of blood for prostate-specific antigens (PSA; a protein produced by prostate cells).
Radical prostatectomy, a surgical procedure to remove the prostate gland and some of the surrounding tissue, is one of the treatment options widely used in men with early-stage prostate cancer. However, 30 to 40% of these patients experience an increase in PSA levels after surgery (defined as biochemical failure), indicating the possibility of cancer recurrence and are often submitted to radiation therapy treatment.
In this study, preserved tumor samples from 43 patients with prostate cancer who had undergone radiation therapy after radical prostatectomy were analyzed; follow-up data of more than 4 years was available for these particular patients. RNA was isolated from the samples and analyzed for the expression of eight hundred different microRNAs (miRNAs), small non-coding RNA molecules that play essential roles in the regulation of gene expression.
Researchers found 88 miRNAs associated with increased PSA levels after prostatectomy, which could be divided into two groups: one where miRNAs correlated well with early recurrence (within 3 years after surgery) and a second one with miRNAs that correlated with late recurrence (more than 3 years after surgery). Interestingly, 9 miRNAs were found to be associated to biochemical failure after radiation therapy, especially two miRNAs — miR-601 and miR-4516.
“This study is the first to demonstrate that miRNA expression in tumor cells correlates with outcome after salvage radiation therapy, paving the way for the potential use of miRNA biomarkers in prostate cancer treatment,” said the study’s first author Dr. Erica Hlavin Bell in a news release.
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Based on their findings, the research team developed a predictive model for prostate cancer biochemical recurrence that comprised information on miR-601 and miR-4516, the Gleason score (a system used to help predict the prognosis of prostate cancer and guide therapy) and lymph node status. This new model might help identify patients at risk of early or late recurrence after radical prostatectomy, and those who should be treated with radiation therapy in case of recurrence after prostate removal.
“If validated by further studies, these findings could change clinical practice and improve the care of prostate-cancer patients,” noted the study’s senior author Dr. Arnab Chakravarti. “Men found to have aggressive disease at the time of prostatectomy could be offered additional treatment with radiation therapy to prevent recurrence, while sparing men with slow-growing tumors,”
“These findings are important because it is currently hard to distinguish early which patients will benefit from radiation therapy following radical prostatectomy and which will receive no benefit,” explained Dr. Bell. “Our novel miRNA panel might also shed light on the underlying mechanisms of treatment resistance in prostate cancer.”
