A Molecular Signature of Circulating MicroRNA Can Predict Osteolytic Bone Disease in Multiple Myeloma

Παπανώτα, Αριστέα-Μαρία; Tsiakanikas, Panagiotis; Kontos, Christos K.; Malandrakis, Panagiotis; Liacos, Christine‐Ivy; Ntanasis‐Stathopoulos, Ioannis; Kanellias, Nikolaos; Gavriatopoulou, Maria; Kastritis, Efstathios; Avgeris, Margaritis; Scorilas, Andreas; Terpos, Evangelos

doi:10.3390/cancers13153877

Cited by 14 publications

(10 citation statements)

References 65 publications

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“…Recently, Papanota et al identified let-7b-5p, miR-143-3p, miR-17-5p, miR-214-3p and miR-335-5p as associated with osteolytic bone disease in MM. Both studies are complementary as they use distinct miRNA panels, and contribute to reach the goal of finding novel non-invasive markers for osteolytic lesions [ 41 ]. Interestingly, Kapinas et al showed that miR-29c-3p is highly expressed in fully mature and mineralized mouse-derived osteoblasts [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating microRNAs Correlate with Multiple Myeloma and Skeletal Osteolytic Lesions

Moura

Abreu

Cunha

et al. 2021

Cancers

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Multiple myeloma (MM) is the second most frequent hematological disease and can cause skeletal osteolytic lesions. This study aims to evaluate the expression of circulating microRNAs (miRNAs) in MM patients and to correlate those levels with clinicopathological features, including bone lesions. A panel of miRNAs associated with MM onset and progression, or with bone remodeling, was analyzed in the plasma of 82 subjects (47 MM patients; 35 healthy controls). Results show that miR-16-5p, miR-20a-5p, and miR-21-5p are differently expressed between MM patients and healthy controls. Receiver operating characteristic analyses indicate that their combined expression has potential as a molecular marker (Area Under the Curve, AUC of 0.8249). Furthermore, significant correlations were found between the analyzed miRNAs and disease stage, treatment, β2 microglobulin, serum albumin and creatinine levels, but not with calcium levels or genetic alterations. In this cohort, 65.96% of MM patients had bone lesions, the majority of which were in the vertebrae. Additionally, miR-29c-3p was decreased in patients with osteolytic lesions compared with patients without bone disease. Interestingly, circulating levels of miR-29b-3p correlated with cervical and thoracic vertebral lesions, while miR-195-5p correlated with thoracic lesions. Our findings suggest circulating miRNAs can be promising biomarkers for MM diagnosis and that their levels correlate with myeloma bone disease and osteolytic lesions.

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Section: Discussionmentioning

confidence: 99%

Circulating microRNAs Correlate with Multiple Myeloma and Skeletal Osteolytic Lesions

Moura

Abreu

Cunha

et al. 2021

Cancers

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“…MM ranks second in hematological malignancies, which is considered to be incurable at present (2). About 80%-90% of MM patients will exhibit different degrees of MM-related bone diseases (3). The severity of bone disease increases mortality (4).…”

Section: Introductionmentioning

confidence: 99%

The Apparent Diffusion Coefficient of Diffusion-Weighted Whole-Body Magnetic Resonance Imaging Affects the Survival of Multiple Myeloma Independently

et al. 2022

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BackgroundDiffusion-weighted whole-body MRI (DW-MRI) is increasingly used to evaluate bone diseases of multiple myeloma (MM), but there is lack of quantitative indicator for DW-MRI to reflect the prognosis of MM. Apparent diffusion coefficient (ADC) values in DW-MRI has potential correlations between some indexes of MM, but the influence of ADC on MM survival needs to be further verified.MethodsA total of 381 newly diagnosed MM patients were enrolled in the study to analyze the effect of ADC values in DW-MRI on progression-free survival (PFS) and overall survival (OS). The Kaplan–Meier method was used to perform univariate survival analysis, and the Cox proportional hazards model was used for multivariate analysis. In addition to the ADC value, genetic and serological indexes were also included.ResultsThe survivals were observed in univariate ADC stratification with median PFS of 52.0, 45.0, 34.0, and 26.0 months (the unit of ADC value was 10−3 mm2/s; the ADC ranges were ADC < 0.4886, 0.4886 ≤ ADC < 0.6545, 0.6545 ≤ ADC < 0.7750, and ADC ≥ 0.7750; 95% CI, 43.759–62.241, 46.336–53.664, 39.753–46.247, and 27.812–32.188). The OS were 81.0, 61.0, 47.0, and 36.0 months (p < 0.001; 95% CI, 71.356–82.644, 67.630–70.370, 57.031–60.969, and 36.107–43.893). In Cox proportional hazards model, the ADC value was considered to be an independent risk factor affecting PFS and OS of MM (both p < 0.001).ConclusionsThis study supports that ADC in DW-MRI may independently stratify MM patients and better predict their prognosis. The combined use of DW-MRI and other parameters allows more accurate evaluation of MM survival.Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=49012, ChiCTR2000029587.

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“…Within this prism, scientific research is currently guided towards the investigation of their role in the pathophysiology of malignancy, as well as their putative role as diagnostic and prognostic biomarkers [ 14 ]. The role of miRNAs and other small non-coding RNAs in multiple myeloma and its associated bone disease is a current topic of scientific interest [ 13 , 15 , 16 , 17 ]. In this study, we investigated the role of a group of miRNAs with an established role in human malignancy in MM and proved their association with the clinicopathological characteristics and the disease outcome of MM patients.…”

Section: Discussionmentioning

confidence: 99%

A Cancer-Related microRNA Signature Shows Biomarker Utility in Multiple Myeloma

Παπανώτα

Karousi

Kontos

et al. 2021

IJMS

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Multiple myeloma (MM) is the second most common hematological malignancy, arising from terminally differentiated B cells, namely plasma cells. miRNAs are small non-coding RNAs that participate in the post-transcriptional regulation of gene expression. In this study, we investigated the role of nine miRNAs in MM. CD138+ plasma cells were selected from bone marrow aspirates from MM and smoldering MM (sMM) patients. Total RNA was extracted and in vitro polyadenylated. Next, first-strand cDNA synthesis was performed using an oligo-dT–adapter primer. For the relative quantification of the investigated miRNAs, an in-house real-time quantitative PCR (qPCR) assay was developed. A functional in silico analysis of the miRNAs was also performed. miR-16-5p and miR-155-5p expression was significantly lower in the CD138+ plasma cells of MM patients than in those of sMM patients. Furthermore, lower levels of miR-15a-5p, miR-16-5p, and miR-222-3p were observed in the CD138+ plasma cells of MM patients with osteolytic bone lesions, compared to those without. miR-125b-5p was also overexpressed in the CD138+ plasma cells of MM patients with bone disease that presented with skeletal-related events (SREs). Furthermore, lower levels of miR-223-3p were associated with significantly worse overall survival in MM patients. In conclusion, we propose a miRNA signature with putative clinical utility in MM.

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A Molecular Signature of Circulating MicroRNA Can Predict Osteolytic Bone Disease in Multiple Myeloma

Cited by 14 publications

References 65 publications

Circulating microRNAs Correlate with Multiple Myeloma and Skeletal Osteolytic Lesions

Circulating microRNAs Correlate with Multiple Myeloma and Skeletal Osteolytic Lesions

The Apparent Diffusion Coefficient of Diffusion-Weighted Whole-Body Magnetic Resonance Imaging Affects the Survival of Multiple Myeloma Independently

A Cancer-Related microRNA Signature Shows Biomarker Utility in Multiple Myeloma

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