Prostate cancer is one of the most common types of cancer in men in the United States. Every ninth man is diagnosed during his lifetime. When diagnosed, a patient's disease is graded from 1 to 5 based on aggressiveness, with 5 being the most aggressive. Individuals with Grade 4/5 disease are at greatest risk for poor outcomes or death from the disease. However, there are no immunological or genomic indicators that can help doctors determine the best course of treatment for this group of patients.
Researchers at the Moffitt Cancer Center, led by Kosj Yamoah, Ph.D., Associate Member and Director of Research on Cancer Differences in the Radiation Oncology and Cancer Epidemiology Departments, hope to change that. The team conducted studies to determine whether genomic heterogeneity in tumors from Grade 4/5 prostate cancer patients can be used to identify patient subgroups who are at greater risk of fatal outcomes and who may benefit from targeted treatment strategies. Their results were published in the journal European Urology.
Their studies focused on transcriptomic interactions between the Tumor Immune Content Score and the Decipher Score, a 22-gene classifier that provides a score that predicts the likelihood of cancer spreading. Researchers analyzed data from 8,071 prostate cancer patient samples of each grade of disease (6,071 prostatectomy and 2,000 previously untreated patients) in the registry of the Decipher Genomics Resource Information Database (GRID). Each patient sample was also given an immune content score (ICS), which was derived using the mean expression of 264 immune cell-specific genes.
The samples were divided into four different immunogenomic subgroups based on their results: ICS high / decryption high, ICS low / decryption high, ICS high / decryption low, and ICS low / decryption low. The researchers found that approximately 25% of all Grade 4/5 patient samples were in the ICS High / Decipher High subgroup.
The ICS-High / Decipher High patient samples were further examined for the association between immunogenomic subtypes and radiation response signatures. They found that the ICS High / Decipher High subgroup were genomically more sensitive to radiation, meaning that these tumors would respond well to radiation therapy. This subgroup also had a higher frequency of T cells and monocytes / macrophages. However, the research team says more research is needed to uncover the biological mechanisms behind this association.
Our results will help subtype aggressive prostate cancer patients who may benefit from combined immuno-radiotherapy modalities. "
Kosj Yamoah, M.D., Ph.D., Moffitt Cancer Center Researcher
Although the results may not be applicable to other tumor genome platforms at this time, the Decipher GRID platform is routinely used in clinical care nationwide and the results can be easily validated in various ongoing clinical trials and the promise of practice to change the near future.
H. Lee Moffitt Cancer Center & Research Institute
Yamoah, K. et al. (2020) Novel transcriptomic interactions between immune content and genome classifier predict fatal outcomes in high-grade prostate cancer. European urology. doi.org/10.1016/j.eururo.2020.11.038.