Article Figures & Data
Figures
- Figure 1.
miRNA expression profiles in NCs, pPCL, and multiple myeloma patients. A, dendrogram of the 4 NCs, 18 pPCL, and 39 multiple myeloma samples clustered according to the expression profiles of the 76 most variable miRNAs. Specific characteristics are enriched in colored sub-branches: pink, NC; grey, multiple myeloma; blue, PCL; orange, t(14;16) or t(14;20) samples; green, t(4;14) samples. B, heatmap of the 26 miRNAs previously identified as distinctive of multiple myeloma TC groups (16) in multiple myeloma and pPCL patients. Multiple myeloma patients are grouped on the basis of TC classification; pPCL samples are ordered according to the IGH translocation type.
- Figure 2.
Kaplan–Meier estimated progression-free survival curves for miR-22 (A) and miR-146a (B), and overall survival curves for miR-92a (C) and miR-330-3p (D) in pPCL cohorts. The samples have been stratified into 2 groups (dashed line: high expression; solid line: low expression) according to the thresholds on sorted expression profiles that led to the highest hazard ratio.
- Figure 3.
Effects of miRNA manipulation on survival of multiple myeloma cell lines. MTT survival assay was conducted in NCI-H929 (A) and RPMI-8226 (B) cells at the indicated time points after transfection with miRNA mimics/inhibitors or scrambled controls (NC). Results are expressed as a percentage of viable cells as compared with control. Quantitative RT-PCR of miR-22 (C) and miR-126 (E) in NCI-H929 cells, and miR-146a (D) and miR-330-3p (F) in RPMI-8226 cells after transfection with corresponding miRNA mimics/inhibitors or scrambled controls. Raw Ct values were normalized to RNU44 housekeeping snoRNA. All the P values obtained using 2-tailed t test were < 0.0001. Results from a representative experiment are shown.
Tables
- Table 1.
PPCL and MM patient characteristics
Genetic lesion Frequency in pPCL cases pos/tested (%) Frequency in the present multiple myeloma series pos/tested (%) P Expected frequency in multiple myeloma (17) del(13q) 17/23 (74%) 22/39 (56%) ns 50% del(17p) 8/23 (35%) 2/39 (5%) 0.004 10% 1q gain 10/21 (48%) 19/37 (51%) ns 40% del(1p) 8/21 (38%) Na 30% (51) t(11;14) 9/23 (39%) 9/39 (23%) ns 15% t(4;14) 3/23 (13%) 7/39 (18%) ns 15% t(14;16) 7/23 (30%) 2/39 (5%) 0.01 6–7% t(14;20) 1/21 (5%) 1/39 (3%) ns 2% NOTE: Significance of the difference of frequencies between pPCL and multiple myeloma cases analyzed here was assessed by Fisher exact test.
Abbreviations: Na, not available; ns, not significant.
- Table 2.
Molecular and clinical data of pPCL patients analyzed for global miRNA expression
Code Age Sex PP del(13q)a del(17p)a 1q gaina del(1p)a t(11;14)a t(4;14)a t(14;16)a t(14;20)a Hb (g/dL) LDH (UI/L) Creatinine (mg/dL) ASCTb Response PFS, mo OS, mo PFS statusc OS statusd PCL-016 57 F Gκ 1 0 1 1 0 0 1 0 11.9 513 0.9 1 CR 31 31 0 0 PCL-017 68 F Gκ 1 1 1 1 0 0 1 0 8.4 1178 0.9 0 CR 10 12 1 1 PCL-018 59 F κ 1 1 0 0 1 0 0 0 9.2 1528 0.5 1 NR 2 32 1 0 PCL-019 67 F Mκ 1 1 1 1 0 0 1 0 7.6 1969 1.6 0 NR 0 13 1 1 PCL-020 79 F Gλ 0 0 1 0 0 0 0 0 8.9 350 2.6 0 PR 16 19 1 1 PCL-021 48 M Gλ 1 0 1 0 0 1 0 0 7.3 137 2.3 1 VGPR 21 27 1 0 PCL-022 50 M Gκ 1 1 0 1 1 0 0 0 13.2 303 1.3 1 CR 26 26 0 0 PCL-023 60 M Gκ 1 1 1 1 0 0 1 0 9.5 433 2 0 NR 0 1 1 1 PCL-026 59 M Gκ 1 0 1 0 0 0 1 0 7.4 195 1.7 1 VGPR 24 24 0 0 PCL-027 65 M λ 0 1 0 0 1 0 0 0 8.5 221 1.2 1 CR 23 23 0 0 PCL-028 57 F κ 1 0 0 0 1 0 0 0 9.2 324 1.5 0 NR 0 2 1 1 PCL-029 51 M Aλ 0 0 0 0 0 0 1 0 9.4 670 2.3 1 NR 0 14 1 0 PCL-030 52 F κ 1 1 0 1 0 0 0 1 8.4 837 0.9 1 PR 2 22 1 0 PCL-032 65 F Gκ 1 0 1 0 0 1 0 0 na na na na na na na na na PCL-034 59 F Gλ 1 0 na na 0 1 0 0 8 326 0.6 1 PR 13 13 0 0 PCL-035 76 F κ 0 0 0 0 1 0 0 0 7.1 917 0.6 0 VGPR 10 10 0 0 PCL-036 71 M Gκ 1 0 0 0 1 0 0 0 8.9 301 0.8 0 PR 9 9 0 0 PCL-037 72 M Aλ 1 0 0 0 1 0 0 0 10.2 513 1.7 0 NR 0 2 1 1 Abbreviations: PP, paraprotein; Hb, hemoglobin; LDH, lactate dehydrogenase; ASCT, autologous stem cell transplantation; CR, complete response; VGPR, very good partial response; PR, partial response; NR, no response; na, not available.
- Table 3.
Differentially expressed miRNAs in pPCL compared with multiple myeloma samples
miRNAa, b SAM scorec miRNAa, b SAM scorec has-miR-21 7.34 hsa-miR-513b −5.75 has-miR-301a 5.13 hsa-miR-513a-5p −5.35 has-miR-374a 4.98 hsa-miR-494 −4.61 has-miR-330-3p 4.79 hsa-miR-513c −4.47 has-miR-454 4.71 hsa-miR-638 −4.06 has-miR-142-3p 4.68 hsa-miR-193b* −4 has-miR-155* 4.38 hsa-miR-1224-5p −3.61 has-miR-301b 4.29 hsa-miR-193a-5p −3.57 has-miR-140-5p 4.09 hsa-miR-222 −3.5 has-miR-18a 4.03 hsa-miR-145 −3.49 has-miR-99a 3.95 hsa-miR-23a* −3.46 has-miR-590-5p 3.95 hsa-miR-221 −3.4 has-miR-362-3p 3.94 hsa-miR-139-3p −3.37 hsa-miR-155 3.91 hsa-miR-423-5p −3.13 hsa-miR-7-1* 3.9 hsa-miR-1226* −3.08 hsa-miR-21* 3.47 hsa-miR-126 −3.05 hsa-miR-628-5p 3.32 hsa-miR-1225-5p −3 hsa-miR-20a* 3.22 hsa-let-7a −2.95 hsa-miR-18b 3.17 hsa-miR-572 −2.91 hsa-miR-19a 3.15 hsa-miR-671-5p −2.91 hsa-miR-29b-1* 3.1 hsa-miR-663 −2.89 hsa-miR-660 3.07 hsa-miR-765 −2.86 hsa-miR-424 2.93 hsa-miR-874 −2.84 hsa-miR-142-5p 2.81 hsa-miR-188-5p −2.8 hsa-miR-100 2.76 hsa-miR-370 −2.8 hsa-miR-103 2.59 hsa-miR-636 −2.77 hsa-miR-532-5p 2.56 hsa-miR-135a* −2.71 hsa-miR-181d 2.56 hsa-miR-345 −2.68 hsa-miR-7 2.54 hsa-miR-34c-3p −2.55 hsa-miR-26b 2.53 hsa-miR-1234 −2.52 hsa-miR-125b 2.53 hsa-miR-193b −2.47 hsa-miR-340 2.52 hsa-miR-221* −2.46 hsa-miR-374b 2.52 hsa-miR-1229 −2.46 hsa-miR-362-5p 2.49 hsa-miR-877* −2.38 hsa-miR-20b 2.48 hsa-miR-625* −2.34 hsa-miR-98 2.46 hsa-miR-324-3p −2.3 hsa-miR-551b 2.45 hsa-miR-96 −2.21 hsa-miR-181a* 2.33 hsa-miR-148a −2.19 hsa-miR-505* 2.3 hsa-miR-483-5p −2.17 hsa-miR-542-3p 2.27 hsa-miR-1228 −2.16 hsa-miR-210 2.18 hsa-miR-223 −2.14 hsa-miR-500* 2.15 -
↵amiRNAs in bold are those whose trend of expression from multiple myeloma to pPCL was significantly maintained (Jonckheere–Terpstra test, P < 0.005) when considering the healthy controls.
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↵bmiRNAs in italic are those that are differentially expressed between pPCL from proprietary cohort and multiple myeloma cases from GEO series GSE17306.
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↵cUp- and downregulated miRNAs are ordered according to SAM scores.
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Supplementary Data
Files in this Data Supplement:
- Supplementary Methods - PDF file - 39K
- Supplementary Figure 1 - PDF file - 358K, MiRNA expression profiles in pPCL patients.
- Supplementary Figure 2 - PDF file - 395K, Expression plots and functional annotations charts of miRNAs identified as differentially expressed between pPCL and MM patients.
- Supplementary Figure 3 - PDF file - 199K, Mir-301a/b ACVR1 anticorrelation in MM.
- Supplementary Figure 4 - PDF file - 133K, Differentially expressed miRNAs identified by supervised analysis of pPCL patients stratified according to response rate.
- Supplementary Figure 5 - PDF file - 29K, Multivariate analysis comparing each of the four miRNA-model (A: miR-22, B: miR-146a, C: miR-92a, D: miR-330-3p) with biological and molecular variables in pPCL series.
- Supplementary Table 1 - PDF file - 22K, Results of correlation analysis between miRNA expression and copy number.
- Supplementary Table 2 - PDF file - 39K, Anticorrelation results and functional annotations analysis of differentially expressed miRNAs between pPCL and MM patients.
Volume 19, Issue 12
