Circulating microRNA as Biomarkers in Hematological Malignancies

Stanková, M; Kubaczková, Veronika; Sedlaříková, Lenka; Ševčı́ková, Sabina

doi:10.1007/978-3-0348-0955-9_5

Cited by 4 publications

(5 citation statements)

References 52 publications

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“…Recent evidence showed distinct miRNA signatures in the blood that arises from tumor burden [10, 23, 24]. These circulating miRNAs are highly stable, resistant to degradation, and have potential to be used as a non-invasive novel therapeutic strategy [23, 25]. Additionally, there have also been distinct circulating miRNAs associated with age-related changes that can impact a variety of diseases included DLBCL [26–28].…”

Section: Introductionmentioning

confidence: 99%

A Circulating microRNA Signature Predicts Age-Based Development of Lymphoma

et al. 2017

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Extensive epidemiological data have demonstrated an exponential rise in the incidence of non-Hodgkin lymphoma (NHL) that is associated with increasing age. The molecular etiology of this remains largely unknown, which impacts the effectiveness of treatment for patients. We proposed that age-dependent circulating microRNA (miRNA) signatures in the host influence diffuse large B cell lymphoma (DLBCL) development. Our objective was to examine tumor development in an age-based DLBCL system using an inventive systems biology approach. We harnessed a novel murine model of spontaneous DLBCL initiation (Smurf2-deficient) at two age groups: 3 and 15 months old. All Smurf2-deficient mice develop visible DLBCL tumor starting at 15 months of age. Total miRNA was isolated from serum, bone marrow and spleen and were collected for all age groups for Smurf2-deficient mice and age-matched wild-type C57BL/6 mice. Using systems biology techniques, we identified a list of 10 circulating miRNAs being regulated in both the spleen and bone marrow that were present in DLBCL forming mice starting at 3 months of age that were not present in the control mice. Furthermore, this miRNA signature was found to occur circulating in the blood and it strongly impacted JUN and MYC oncogenic signaling. In addition, quantification of the miRNA signature was performed via Droplet Digital PCR technology. It was discovered that a key miRNA signature circulates throughout a host prior to the formation of a tumor starting at 3 months old, which becomes further modulated by age and yielded calculation of a ‘carcinogenic risk score’. This novel age-based circulating miRNA signature may potentially be leveraged as a DLBCL risk profile at a young age to predict future lymphoma development or disease progression as well as for potential innovative miRNA-based targeted therapeutic strategies in lymphoma.

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Section: Introductionmentioning

confidence: 99%

A Circulating microRNA Signature Predicts Age-Based Development of Lymphoma

et al. 2017

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“…miRNAs are small non-coding RNAs impacting post-transcriptional gene expression that have shown to have a major impact on lymphoma biology as well as associated therapeutic potential 10,13,19,23 . Furthermore, these miRNAs are in the circulating serum, are stable, and are resistant to degradation 15,19 . Leveraging findings from an initial transgenic lymphoma knockout model 19 , we investigated for the presence of circulating miRNAs in human DLBCL cells, DLBCL PDX models, and sera from DLBCL patients.…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs (miRNA) are small, non-coding RNA of approximately 22 nucleotides that target hundreds of messenger RNAs, regulate proteins, and interact with DNA 9–13 . Due to their small size, circulating miRNAs are stable and resistant to degradation 14,15 . Most literature linking miRNAs and lymphoma have concentrated on one or two different miRNAs that could serve as biomarkers 9–12,16,17 or single miRNA-related treatments 16,17 .…”

Section: Introductionmentioning

confidence: 99%

Identification of Circulating Serum Multi-MicroRNA Signatures in Human DLBCL Models

Beheshti

Stevenson

Vanderburg

et al. 2019

Sci Rep

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There remains a need to identify new sensitive diagnostic and predictive blood-based platforms in lymphoma. We previously discovered a novel circulating microRNA (miRNA) signature in a Smurf2-deficient mouse model that spontaneously develops diffuse large B-cell lymphoma (DLBCL). Herein, we investigated this 10-miRNA signature (miR-15a, let-7c, let-7b, miR-27a, miR-10b, miR-18a, miR-497, miR-130a, miR24, and miR-155) in human lymphoma cell lines, mice engrafted with patient-derived xenografts (PDXs), and DLBCL patient serum samples leveraging systems biology analyses and droplet digital PCR (ddPCR) technology. Overall, 90% of the miRNAs were enriched in PDX DLBCL models and human lymphoma cell lines. Circulating miRNAs from the serum of 86 DLBCL patients were significantly increased compared with healthy controls and had similar patterns to the murine models. Strikingly, miRNAs were identified up to 27-fold higher levels in the serum of PDX-bearing mice and human patients compared with lymphoma cell lysates, suggesting a concentration of these factors over time within sera. Using cut-points from recursive partitioning analysis, we derived a 5-miRNA signature (let-7b, let-7c, miR-18a, miR-24, and miR-15a) with a classification rate of 91% for serum from patients with DLBCL versus normal controls. In addition, higher levels of circulating let-7b miRNA were associated with more advanced stage disease (i.e., III-IV vs. I-II) in DLBCL patients and higher levels of miR-27a and miR-24 were associated with MYC rearrangement. Taken together, circulating multi-miRNAs were readily detectable in pre-clinical cell line and human lymphoma models as well as in DLBCL patients where they appeared to distinguish clinico-pathologic subtypes and disease features.

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“…MicroRNAs (miRNAs) are small noncoding RNA, about 22 base lengths. Since its discovery in 1990, about 2500 miRNAs have been found in human beings 1 . MiRNAs involve in the physiological and pathological processes of many diseases, including cell differentiation, angiogenesis, apoptosis, tumor development, metastasis, and drug resistance 2‐4 .…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs in urine as diagnostic biomarkers for multiple myeloma

Wang

Meng

et al. 2020

Int J Lab Hematology

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Introduction Multiple myeloma (MM) is a hematological malignancy. It is of great clinical significance to screen microRNAs (miRNAs) in urine as noninvasive diagnostic biomarkers for MM. Methods Urinary miRNAs in MM were performed by Agilent Bioanalyzer 2100 and verified by quantitative real‐time PCR (qRT‐PCR). Receiver operator characteristic (ROC) was used to evaluate the diagnostic value of abnormal miRNAs for MM. Progression‐free survival (PFS) of MM was calculated by Kaplan‐Meier. Results In microarray analysis, twelve down‐regulated miRNAs dysregulated in MM. The expression levels of miR‐134‐5p, miR‐6500‐5p, miR‐548q, and miR‐548y were validated. These miRNAs were significantly lower in MM (P < .05), but there was no significant difference between newly diagnosed, relapse, and remission group of MM (P> .05). ROC curve analysis showed that the sensitivity of miR‐134‐5p, miR‐6500‐5p, miR‐548q, and miR‐548y to MM was 91.7%, 100%, 100%, and 91.7%, and the specificity was 66.7%, 75.0%, 75.0%, and 100%, respectively. The four miRNAs were negatively correlated with the total urinary light chain (r = −0.427 P = .030, r = −0.461 P = .018, r = −0.469 P = .016, r = −0.493 P = .011). In addition, miR‐134‐5p, miR‐6500‐5p, and miR‐548q were positively correlated with serum ALB (r = 0.518 P = .006, r = 0.400 P = .039,r = 0.492 P = .009). The expression level of miRNAs had no significant influence on PFS in MM patients (P> .05). Conclusion The results show that miR‐134‐5p, miR‐6500‐5p, miR‐548q, and miR‐548y are potential noninvasive diagnostic biomarkers for MM.

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Circulating microRNA as Biomarkers in Hematological Malignancies

Cited by 4 publications

References 52 publications

A Circulating microRNA Signature Predicts Age-Based Development of Lymphoma

A Circulating microRNA Signature Predicts Age-Based Development of Lymphoma

Identification of Circulating Serum Multi-MicroRNA Signatures in Human DLBCL Models

MicroRNAs in urine as diagnostic biomarkers for multiple myeloma

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