The Prognostic Potential of circRNAs in Multiple Myeloma: Insights From Whole Bone Marrow and Purified Plasma Cells.

Multiple myeloma (MM) is a haematological malignancy with abnormal proliferation of plasma cells in the bone marrow (BM), and MM patients with highly proliferative plasma cells have reduced overall survival. Circular RNAs (circRNAs) are endogenous, non-coding molecules that are promising biomarkers in cancer. Here, we present the largest study of circRNAs in MM to date and explore the prognostic potential of circRNAs and the link between proliferation and circRNA expression in MM. We performed deep total RNA sequencing (RNA-seq) on two cohorts: one cohort consisting of 45 whole BM MM patient samples and 13 healthy controls (HCs), and another cohort consisting of 43 CD138-purified plasma cell MM patient samples. We found that circRNAs are globally upregulated in the whole BM of MM patients compared to HCs. In whole BM, low proliferation and high circRNA levels were associated with a poor prognosis, while in purified plasma cells, low proliferation and high circRNA levels were associated with a favourable prognosis. Individual circRNAs from purified plasma cells were found to be significantly associated with MM patient outcomes and provide additional prognostic value to the proliferative indexes. Together, our findings emphasise the potential of circRNAs as prognostic biomarkers in MM.