Association between BRAF expression in circulating tumor cells and the clinical feature of patients with multiple myeloma.

Multiple myeloma (MM) is the most common hematological malignancy with uncontrolled proliferation of monoclonal plasma cells. Despite treatment improvements, MM remains an incurable disease for most patients. Therefore, promising molecular markers are required for MM treatment decisions. In the present study, we explored the relationship between the BRAF expression in circulating tumor cells (CTCs) and the clinical features of patients with MM. The results showed that CTCs were associated with MM staging, and the expression of BRAF was associated with different CTCs. Moreover, the BRAF gene was correlated with patients' white blood cells, blood albumin levels, and Eastern Cooperative Oncology Group (ECOG) score. BRAF expression positively correlated with total CTCs, hybrid CTCs, and mesenchymal CTCs. Taken together, CTCs tightly correlated with the clinical stages and characteristics of MM. Our findings may provide a promising prognosis biomarker for MM treatment decisions.

Exosomal mRNAs and lncRNAs involved in multiple myeloma resistance to bortezomib.

The bone marrow microenvironment plays an essential role in multiple myeloma (MM) progression. We aimed to explore the alterations of levels of long noncoding RNAs and messenger RNAs (mRNAs), derived from exosomes in peripheral blood, in resistance to bortezomib (Btz) of MM patients. Peripheral blood samples were collected from five Btz-resistant and five Btz-sensitive MM patients. Exosomes in patients' peripheral blood were enriched, and the profiles of long noncoding RNAs (lncRNAs) and mRNAs in exosomes were determined using deep sequencing. Bioinformatics analysis was performed to explore biological function. MTS was employed to determine the viability of Roswell Park Memorial Institute (RPMI) 8226 and LP-1 cells incubated with exosomes derived from Btz-resistant patients. Quantitative polymerase chain reaction (qPCR) was used to evaluate the levels of exosomal FFAR1, SP9, HIST1H2BG, and ITIH2. Incubation with Btz-resistant patient-derived exosomes significantly increased the viability of Btz-treated RPMI 8226 and LP-1 cells in a dose-dependent manner. We identified 482 lncRNAs and 2099 mRNAs deregulated in exosomes of the Btz-resistance group; and 78 mRNAs were enriched in DR-related pathways, including mammalian target of rapamycin, platinum drug resistance, and the cAMP and phosphoinositide 3-kinase-Akt signaling pathways. qPCR results verified the increases in FFAR1 and SP9 and decreases in HIST1H2BG and ITIH2 in Btz-resistant patient-derived exosomes. Moreover, exosomal FFAR1 and SP9 exhibited potential as independent prognostic indicators of survival of MM patients. Our study reveals significant dysregulation of exosomal RNA components in the Btz-resistant group of MM patients as well as several mRNAs that may be used as biomarkers of prognosis of MM patients that are resistant to Btz.