A Cancer-Related microRNA Signature Shows Biomarker Utility in Multiple Myeloma
Abstract
:1. Introduction
2. Results
2.1. Development and Optimization of Real-Time qPCR Assays
2.2. miR-16-5p and miR-155-5p Levels Are Significantly Lower in MM Patients Compared to sMM Patients
2.3. Association of the Expression of Three of the Investigated miRNAs with MM Bone Disease (MMBD)
2.4. miR-125b-5p Levels Are Associated with MMBD Severity
2.5. miR-223-3p Offers a Putative Prognostic Value in MM
2.6. In Silico Functional miRNA Analysis
3. Discussion
4. Materials and Methods
4.1. Study Participants
4.2. CD138+ Plasma Cell Selection
4.3. RNA Isolation, In Vitro Polyadenylation, and Reverse Transcription
4.4. Quantification of miRNA Expression Using Real-Time qPCR
4.5. Biostatistics
4.6. Functional In Silico Analysis for miRNA Target Prediction and KEGG Pathway Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | Mean ± S.E. 1 | Range | Percentiles | ||
---|---|---|---|---|---|
25th | 50th (Median) | 75th | |||
miR-16-5p levels (RQU 2) | |||||
in sMM patients | 44.58 ± 14.04 | 0.004–167.3 | 2.94 | 10.16 | 82.20 |
in MM patients | 13.77 ± 4.10 | 0.046–264.5 | 1.77 | 3.54 | 10.26 |
miR-155-5p levels (RQU 2) | |||||
in sMM patients | 1285.7± 539.8 | <0.001–6097.5 | 15.06 | 182.8 | 1402.7 |
in MM patients | 366.0 ± 167.6 | <0.001–9738.0 | 2.21 | 23.05 | 130.3 |
miR-15a-5p levels (RQU 2) | |||||
in MM patients without osteolytic lesions | 29.93 ± 12.66 | 0.008–181.0 | 1.76 | 7.30 | 22,29 |
in MM patients with osteolytic lesions | 7.71 ± 3.25 | 0.003–122.9 | 0.37 | 1.85 | 6.76 |
miR-16-5p levels (RQU 2) | |||||
in MM patients without osteolytic lesions | 19.27 ± 7.18 | 0.92–109.9 | 3.07 | 7.06 | 15.68 |
in MM patients with osteolytic lesions | 7.49 ± 2.39 | 0.12–82.77 | 1.39 | 2.64 | 8.50 |
miR-222-3p levels (RQU 2) | |||||
in MM patients without osteolytic lesions | 10.95 ± 3.17 | 0.006–54.28 | 1.56 | 8.03 | 15.57 |
in MM patients with osteolytic lesions | 6.03 ± 1.65 | 0.007–43.54 | 0.06 | 2.56 | 6.55 |
miR-125b-5p levels (RQU 2) | |||||
in MM patients without SREs 3 | 15.00 ± 8.12 | 0.001–139.8 | 0.17 | 1.17 | 15.62 |
in MM patients with SREs 3 | 39.39 ± 12.72 | 0.12–247.7 | 5.96 | 26.28 | 44.75 |
Univariate Analysis | Multivariate Analysis | |||||
---|---|---|---|---|---|---|
Covariate | HR 1 | BCa 4 Bootstrap 5 95% CI 2 | Bootstrap5 p Value 3 | HR 1 | BCa 4 Bootstrap 5 95% CI 2 | Bootstrap5 p Value 3 |
miR-223-3p expression status | ||||||
Positive | 1.00 | 1.00 | ||||
Negative | 3.11 | 0.95–22.15 | 0.034 | 3.34 | 0.71–2.6 × 105 | 0.046 |
R-ISS 6 (ordinal) | 3.31 | 1.05–13.22 | 0.025 | 3.14 | 1.05–21.17 | 0.021 |
Variable | Number of MM Patients (%) |
---|---|
Gender | |
Male | 44 (57.9%) |
Female | 32 (42.1%) |
Myeloma type | |
IgG | 44 (57.9%) |
IgA | 17 (22.4%) |
IgD | 2 (2.6%) |
Light chain | 10 (13.2%) |
Non-secretory | 2 (2.6%) |
Missing data | 1 (1.3%) |
ISS 1 stage | |
I | 15 (19.7%) |
II | 25 (32.9%) |
III | 34 (44.8%) |
Missing data | 2 (2.6%) |
R-ISS 2 stage | |
I | 11 (14.5%) |
II | 40 (52.6%) |
III | 18 (23.7%) |
Missing data | 7 (9.2%) |
Bone disease | |
No | 22 (28.9%) |
Yes | 50 (65.8%) |
Missing data | 4 (5.3%) |
WBLDCT 3 osteolysis | |
No | 18 (23.7%) |
Yes | 38 (50.0%) |
Missing data | 20 (26.3%) |
SREs 4 (38 MM patients) | |
No | 18 (47.4%) |
Yes | 20 (52.6%) |
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Papanota, A.-M.; Karousi, P.; Kontos, C.K.; Artemaki, P.I.; Liacos, C.-I.; Papadimitriou, M.-A.; Bagratuni, T.; Eleutherakis-Papaiakovou, E.; Malandrakis, P.; Ntanasis-Stathopoulos, I.; et al. A Cancer-Related microRNA Signature Shows Biomarker Utility in Multiple Myeloma. Int. J. Mol. Sci. 2021, 22, 13144. https://doi.org/10.3390/ijms222313144
Papanota A-M, Karousi P, Kontos CK, Artemaki PI, Liacos C-I, Papadimitriou M-A, Bagratuni T, Eleutherakis-Papaiakovou E, Malandrakis P, Ntanasis-Stathopoulos I, et al. A Cancer-Related microRNA Signature Shows Biomarker Utility in Multiple Myeloma. International Journal of Molecular Sciences. 2021; 22(23):13144. https://doi.org/10.3390/ijms222313144
Chicago/Turabian StylePapanota, Aristea-Maria, Paraskevi Karousi, Christos K. Kontos, Pinelopi I. Artemaki, Christine-Ivy Liacos, Maria-Alexandra Papadimitriou, Tina Bagratuni, Evangelos Eleutherakis-Papaiakovou, Panagiotis Malandrakis, Ioannis Ntanasis-Stathopoulos, and et al. 2021. "A Cancer-Related microRNA Signature Shows Biomarker Utility in Multiple Myeloma" International Journal of Molecular Sciences 22, no. 23: 13144. https://doi.org/10.3390/ijms222313144