Contributions
Abstract: EP958
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Multiple myeloma (MM) is an incurable plasma cell (PC) malignancy with genetic heterogeneity and variable therapeutic outcome. Despite the availability of several prognostic markers, treatment failure remains an unpredictable challenge in MM. Recent studies have identified serum/plasma-microRNA as a clinically relevant biomarker in many malignancies, including MM. The prognostic impact of serum miRNAs has been studied in MM. However, its role in the prediction of therapeutic response is still unknown. We studied serum-microRNA profiling by deep-sequencing in newly diagnosed-MM (NDMM) and evaluated its clinical utility.
Aims
To study the expression profile of plasma/serum microRNAs and identify clinically relevant dysregulated microRNAs.
Methods
The study cohort included 65-NDMM (age range, 27-74; median-54 years) treated with Bortezomib-based therapy and could not be treated with autologous stem cell transplant due to various reasons as well as 10 age-matched controls. Serum/plasma microRNAs profiling was performed by deep sequencing on BGISEQ-500 platform in diagnostic samples. The initial therapeutic response was monitored at the end of 4 and 8 cycles of Bortezomib-based therapy. The standard prognostication, including ISS staging, cytogenetics, and clonal-PCs assessment in bone marrow samples by flow cytometry, was performed.
Results
RNA-seq data analysis identified a total of 1098 microRNA. Differential expression analysis revealed 37 microRNA dysregulated in MM (fold change≥2, p-adjusted<0.05), greater majority being up-regulated (31/37). 14/37 have been previously reported in MM pathogenesis. Top dysregulated microRNAs (Log2 fold change≥4, p-adjusted<0.05) included hsa-miR-92b-5p/hsa-miR-4775/hsa-miR-642a-5p/hsa-miR-103a-2-5p/hsa-miR-296-5p/hsa-miR-4665-5p/hsa-miR-4772-3p/hsa-miR-214-3p/hsa-miR-370-5p/hsa-miR-185-3p/hsa-miR-769-5p/hsa-miR-365a-3p/hsa-miR-365b-3p/hsa-miR-6843-3p. Among them, hsa-miR-629-3p was found significantly associated with poor initial therapeutic response. Additionally, hsa-miR-103a-2-5p, hsa-miR-296-5p, hsa-miR-4772-3p, hsa-let-7i-3p, hsa-miR-148a-3p and hsa-miR-328-3p are significantly associated with an increased (>95%) clonal PCs; hsa-miR-103a-2-5p, hsa-miR-625-3p, hsa-miR-342-3p, hsa-miR-532-3p and hsa-miR-625-3p demonstrated significant association with the ISS-stage-I and III. We also found a strong association of hsa-miR-103a-2-5p, hsa-miR-199a-3p and hsa-miR-204-5p with chromosome 17p deletion.
Conclusion
We have identified 37 dysregulated serum-microRNA specific to and targeting functionally relevant pathways in MM, including p53-mediated signaling and proteasome-mediated processes. We, for the first-time report an association of hsa-miR-629-3p upregulation with poor initial response to Bortezomib-based therapy. We also report unique miRNAs associated with patients with high tumor burden MM (clonal-PC>95%). Thus, in addition to prognostication and risk stratification, our data demonstrated the value of serum microRNAs in predicting initial response to Bortezomib-based treatment in NDMM.
Keyword(s): Expression profiling, Multiple myeloma, Prognostic
Abstract: EP958
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Biology & Translational Research
Background
Multiple myeloma (MM) is an incurable plasma cell (PC) malignancy with genetic heterogeneity and variable therapeutic outcome. Despite the availability of several prognostic markers, treatment failure remains an unpredictable challenge in MM. Recent studies have identified serum/plasma-microRNA as a clinically relevant biomarker in many malignancies, including MM. The prognostic impact of serum miRNAs has been studied in MM. However, its role in the prediction of therapeutic response is still unknown. We studied serum-microRNA profiling by deep-sequencing in newly diagnosed-MM (NDMM) and evaluated its clinical utility.
Aims
To study the expression profile of plasma/serum microRNAs and identify clinically relevant dysregulated microRNAs.
Methods
The study cohort included 65-NDMM (age range, 27-74; median-54 years) treated with Bortezomib-based therapy and could not be treated with autologous stem cell transplant due to various reasons as well as 10 age-matched controls. Serum/plasma microRNAs profiling was performed by deep sequencing on BGISEQ-500 platform in diagnostic samples. The initial therapeutic response was monitored at the end of 4 and 8 cycles of Bortezomib-based therapy. The standard prognostication, including ISS staging, cytogenetics, and clonal-PCs assessment in bone marrow samples by flow cytometry, was performed.
Results
RNA-seq data analysis identified a total of 1098 microRNA. Differential expression analysis revealed 37 microRNA dysregulated in MM (fold change≥2, p-adjusted<0.05), greater majority being up-regulated (31/37). 14/37 have been previously reported in MM pathogenesis. Top dysregulated microRNAs (Log2 fold change≥4, p-adjusted<0.05) included hsa-miR-92b-5p/hsa-miR-4775/hsa-miR-642a-5p/hsa-miR-103a-2-5p/hsa-miR-296-5p/hsa-miR-4665-5p/hsa-miR-4772-3p/hsa-miR-214-3p/hsa-miR-370-5p/hsa-miR-185-3p/hsa-miR-769-5p/hsa-miR-365a-3p/hsa-miR-365b-3p/hsa-miR-6843-3p. Among them, hsa-miR-629-3p was found significantly associated with poor initial therapeutic response. Additionally, hsa-miR-103a-2-5p, hsa-miR-296-5p, hsa-miR-4772-3p, hsa-let-7i-3p, hsa-miR-148a-3p and hsa-miR-328-3p are significantly associated with an increased (>95%) clonal PCs; hsa-miR-103a-2-5p, hsa-miR-625-3p, hsa-miR-342-3p, hsa-miR-532-3p and hsa-miR-625-3p demonstrated significant association with the ISS-stage-I and III. We also found a strong association of hsa-miR-103a-2-5p, hsa-miR-199a-3p and hsa-miR-204-5p with chromosome 17p deletion.
Conclusion
We have identified 37 dysregulated serum-microRNA specific to and targeting functionally relevant pathways in MM, including p53-mediated signaling and proteasome-mediated processes. We, for the first-time report an association of hsa-miR-629-3p upregulation with poor initial response to Bortezomib-based therapy. We also report unique miRNAs associated with patients with high tumor burden MM (clonal-PC>95%). Thus, in addition to prognostication and risk stratification, our data demonstrated the value of serum microRNAs in predicting initial response to Bortezomib-based treatment in NDMM.
Keyword(s): Expression profiling, Multiple myeloma, Prognostic