Researchers have uncovered that sex-specific dysregulation of exosomal non-coding RNAs may drive different patterns of disease progression of multiple myeloma in male and female individuals, according to findings published in Blood Cancer Journal.
“The same therapies are provided for men and women facing multiple myeloma, but we know men develop the disease more often,” said corresponding author Reza Shahbazi, PhD, Assistant Professor of Medicine at the Indiana University School of Medicine and researcher at the Brown Center for Immunotherapy. “In our research, we found there are key non-coding RNAs that differ between men and women. Those specific targets could help us develop personalized therapies or choose the best therapies for individual patients.”
Background and Study Methods
Multiple myeloma occurs more frequently in men than women; researchers sought to understand why. The team conducted an in-depth molecular analysis of dysregulated exosomal non-coding RNAs in male and female patients with multiple myeloma (n = 24) as well as multiple myeloma cell lines to understand the differences in the underlying molecular mechanisms for men and women with multiple myeloma.
Key Findings
The researchers found alterations in enriched pathways that influence key biological cell processes. Distinct sex-specific expression signatures were also revealed across various states of disease and by different treatment exposures.
They gathered a panel of non-coding RNAs that showed sex-specific expression patterns or that were involved in the enriched pathways, which revealed that exosomes provide enhanced analytical resolution for the detection of non-coding RNAs, which led to the identification of more sensitive and precise transcriptomic alterations.
Sex-specific dysregulation of non-coding RNAs may impact different patterns of disease progression in multiple myeloma, as well as response to therapy.
“Non-coding RNAs end up packaged inside the exosomes to be sent out for a cellular response—so they get packaged inside the cells, and in this case, multiple myeloma cells,” Dr. Shahbazi said. “We identified that the exosomes from male and female patients are totally different, despite commonalities. They carry specific messages that could help us with the diagnosis of the disease. Many of these non-coding RNAs regulate genes involved in immune response, cell growth, and drug resistance, making them potential biomarkers.”
As such, sex-tailored therapeutic strategies using exosomal non-coding RNA profiling to target dysregulated non-coding RNAs could be beneficial for the individualized treatment of male and female patients with multiple myeloma.
Disclosure: Research was supported by funding from the National Institutes of Health. For full disclosures of the study authors, visit nature.com.
