Identification and prognostic prediction of high-risk multiple myeloma by exosomal microRNA

Tian Ying¹Wenjiao Tang¹Chunlan Zhang¹Juan Xu¹Yunfan Yang¹Qinyu Liu¹Xushu Zhong¹Jie Wang¹Caigang Xu^1,2*

• ¹Sichuan University West China Hospital Department of Hematology, Chengdu, China
• ²Chengdu Shangjin Nanfu Hospital, Chengdu, China

Circulating exosomal microRNAs (miRNAs) are gaining traction as novel liquid biopsy biomarkers for the early detection, treatment monitoring, and prognostication of multiple myeloma (MM). Employing RNA sequencing, we identified 20 differentially expressed genes in exosomes isolated from the peripheral blood of 17 newly diagnosed multiple myeloma patients and 8 healthy controls. Utilizing a testing cohort of 60 newly diagnosed MM cases, we developed a diagnostic model based on six miRNAs (hsa-miR-192-5p, hsa-miR-10a-5p, hsa-miR-10b-3p, hsa-miR-148a-3p, hsa-miR-193b-5p, hsa-miR-483-3p) achieving an AUC of 0.94, sensitivity of 0.88, and specificity of 0.94. In a validation cohort of 130 MM patients, we developed a prognostic nomogram that amalgamated the expression levels of three key exosomal miRNAs (hsa-miR-193b-5p, miR-483-3p, and let-7b-5p) with critical clinical variables, which exhibits superior performance compared to the ISS staging