The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients

Abstract

Bortezomib is the first-in-class proteasome inhibitor, commonly used in the treatment of multiple myeloma (MM). The mechanisms underlying acquired bortezomib resistance in MM are poorly understood. Several cell-free miRNAs have been found to be aberrantly regulated in MM patients. The aim of this pilot study was to identify a blood-based miRNA signature that predicts bortezomib-based therapy efficacy in MM patients. Thirty MM patients treated with bortezomib-based regimens were studied, including 19 with refractory disease and 11 who were bortezomib sensitive. Serum miRNA expression patterns were identified with miRCURY LNA miRNA miRNome PCR Panels I+II (Exiqon/Qiagen). Univariate analysis found a total of 21 miRNAs to be differentially expressed in patients with MM according to bortezomib sensitivity. Multivariate logistic regression was created and allowed us to discriminate refractory from sensitive patients with a very high AUC of 0.95 (95%CI: 0.84–1.00); sensitivity, specificity and accuracy were estimated as 0.95, 0.91, and 0.93. The model used expression of 3 miRNAs: miR-215-5p, miR-181a-5p and miR-376c-3p. This study is the first to demonstrate that serum expression of several miRNAs differs between patients who are bortezomib refractory and those who are sensitive which may prove useful in studies aimed at overcoming drug resistance in MM treatment.

microRNAs as the biomarkers of chemotherapy-induced peripheral neuropathy in patients with multiple myeloma

“…The miRNA may also be a marker of the efficacy of bortezomib-based therapy in MM patients. Identification of the expression of miR-215-5p, miR-181a-5p and miR-376c-3p in the blood of MM patients allows to distinguish between susceptible and treatment-resistant patients [14].…”

Circulating miRNAs as Auxiliary Diagnostic Biomarkers for Multiple Myeloma: A Systematic Review, Meta-Analysis, and Recommendations

“…More interestingly, the expression levels of miR-19a, miR-744-5p, miR-143-5p, and miR-92a, had significantly different outcomes in bortezomib-based treatment (22,(65)(66)(67). Patients with higher serum levels of miR-214 had extended overall survival upon bisphosphonate-based therapy (68).…”

The Prognostic Value of Whole-Blood PSMB5, CXCR4, POMP, and RPL5 mRNA Expression in Patients with Multiple Myeloma Treated with Bortezomib

“…All of the patients received bortezomib treatment as first-line treatment or in progression after previous therapy. The participants were classified as either bortezomib-sensitive or bortezomib-refractory, as previously reported, according to their response to bortezomib-based therapy [ 12 , 54 ]. Response to treatment and relapse/progression events were classified according to the IMWG [ 55 , 56 ].…”

“…Although resistance to PIs appears to be acquired through a number of different mechanisms, genetic abnormalities play a key role for most anti-myeloma drugs [ 8 , 10 , 11 , 12 ]. Single-point mutations and modification of gene expression in neoplastic cells refractory to PI have been reported in previous studies [ 11 , 13 , 14 , 15 , 16 ].…”