The Role Of Peripheral Blood Circulating MVs In Multiple Myeloma As A Novel Tumor Biomarker

Objective: To further confirm the correlation of PB circulating MVs(cir MVs) with the clinical features of MM patients and determine whether PB cir MVs could serve as a novel tumor marker for MM bone lesions and kidney dysfunction and for MM diagnosis.Methods: The peripheral blood of newly-diagnosed multiple myeloma patients and healthy donors was obtained in anti-coagulate tubes with EDTA anticoagulant. MVs were isolated using differential centrifugation methods, stained with calcein-AM stain, anti-CD138-PE, anti-CD38-APC, anti-CD19-APC/cy7 and anti-CD45-Per CP antibodies, washed and then analyzed using flow cytometry. Then the correlations of the counts of CD138+ cir MVs, CD138+/CD38+ cir MVs, CD138-/CD19+ cir MVs and CD38+/CD45- cir MVs with MM clinical features were analyzed.Results: The levels of CD138+ cir MVs, CD138+/CD38+ cir MVs, CD138-/CD19+ cir MVs and CD38+/CD45- cir MVs in peripheral blood from newly-diagnosed multiple myeloma patients were significantly higher, compared to healthy volunteers. And the counts of CD138+ cir MVs and CD138+/CD38+ cir MVs could serve as a diagnostic biomarker for MM, with area under ROC curve(AUC) of 0.734, 0.906 separately. Significant difference was found between the patients with bone lesions less than 3 and the patients with more than 3 in the counts of CD138+ cir MVs, but not the counts of CD138+/CD38+ cir MVs. In MM kidney dysfunction, the counts of CD138+ cir MVs but not CD138+/CD38+ cir MVs correlated with the level of blood Scr value. The counts of CD138+ cir MVs could serve as a diagnostic biomarker for MM associated bone lesions and kidney dysfunction, with area under ROC curve of 0.734, 0.731, respectively. No obvious correlation could be found between the counts of CD138+ cir MVs and CD138+/CD38+ cir MVs and disease ISS stages, disease types, values of β2-MG, LDH, CRP, serum calcium and albumin, respectively, neither between the counts of CD138-/CD19+ cir MVs or CD38+/CD45-cir MVs and D-S stages, ISS stages, disease types, values of β2-MG, LDH, CRP, serum calcium and albumin..Conclusion: MM-related PB cir MVs with specific markers can be detected using FCM. The counts of cir MVs correlate with MM clinical features and serve as a novel biomarker for MM, MM bone disease and MM kidney dysfunction.