Circulating miR-455-3p, miR-5787, and miR-548a-3p as potential noninvasive biomarkers in the diagnosis of acute graft-versus-host disease: a validation study

Motaei, Jamshid; Kerachian, Mohammad Amin; Mousavi, S. Hossein; Alimoghadam, Kamran; Ghavamzadeh, Ardeshir; Manoochehrabadi, Saba; Ahmadvand, Mohammad; Yaghmaie, Marjan

doi:10.1007/s00277-021-04573-1

Cited by 6 publications

(7 citation statements)

References 57 publications

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“…Higher grades (III‐IV) of aGVHD as well as greater quantities of soluble IL‐17, IL‐9, and IFN‐gamma components have also been associated with higher miR‐155 expression [23]. In yet another instance, miR‐194, miR‐29a, miR‐518f, miR‐153, miR‐548a, and miR‐586 were considerably upregulated in plasma samples of patients who develop aGVHD after HSCT, whereas miR‐5787 and miR‐455 were dramatically downregulated [2, 11, 15, 24, 25]. Besides serving as diagnostic biomarkers, circulating miRNAs also hold promise as prognostic indicators in aGVHD.…”

Section: Discussionmentioning

confidence: 99%

“…Based on previous studies conducted in our research center using RT‐qPCR and miRNA array [14, 15], six miRNAs (miR‐638, miR‐6511b‐5p, miR‐3613‐5p, miR‐455‐3p, miR‐5787, and miR‐548a‐3p) were identified as significant and displayed the largest fold alternations. In this cohort study, every single miRNA was approved employing RT‐qPCR in patient as well as control samples.…”

Section: Methodsmentioning

confidence: 99%

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Diagnosis of Cutaneous Acute Graft‑Versus‑Host Disease Through Circulating Plasma miR‐638, miR‐6511b‐5p, miR‐3613‐5p, miR‐455‐3p, miR‐5787, and miR‐548a‐3p as Prospective Noninvasive Biomarkers Following Allogeneic Hematopoietic Stem Cell Transplantation

Izadifard,

Ahmadvand,

Pashaiefar

et al. 2024

Clinical Transplantation

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BackgroundThere are currently no laboratory tests that can accurately predict the likelihood of developing acute graft‐versus‐host disease (aGVHD), a patient's response to treatment, or their survival chance. This research aimed to establish circulating miRNAs as diagnostic, prognostic, or predictive biomarkers of aGVHD.MethodsIn a prospective cohort, we studied the incidence of cutaneous aGVHD in AML patients undergoing allo‐HSCT at Shariati Hospital in Tehran, Iran during 2020–2023. Patients with cutaneous aGVHD were labeled as the case group, while patients without cutaneous aGVHD were selected as the control group. Accordingly, the expression levels of six significant miRNAs (miR‐638, miR‐6511b‐5p, miR‐3613‐5p, miR‐455‐3p, miR‐5787, miR‐548a‐3p) were evaluated by quantitative reverse transcription–polymerase chain reaction (RTqPCR) in three different time‐points: before transplantation, on day 14 and day 21 after transplantation.ResultsThe levels of plasma miR‐455‐3p, miR‐5787, miR‐638, and miR‐3613‐5p were significantly downregulated, while miR‐548a‐3p, and miR‐6511b‐5p were significantly upregulated in individuals with cutaneous aGVHD in comparison to patients without GVHD. Additionally, the possibility for great diagnostic accuracy for cutaneous aGVHD was revealed by ROC curve analysis of differentially expressed miRNAs (DEMs).ConclusionThe study findings encourage us to hypothesize that the aforementioned miRNAs may contribute to the predominance of aGVHD, particularly low‐grade cutaneous aGVHD.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Diagnosis of Cutaneous Acute Graft‑Versus‑Host Disease Through Circulating Plasma miR‐638, miR‐6511b‐5p, miR‐3613‐5p, miR‐455‐3p, miR‐5787, and miR‐548a‐3p as Prospective Noninvasive Biomarkers Following Allogeneic Hematopoietic Stem Cell Transplantation

Izadifard,

Ahmadvand,

Pashaiefar

et al. 2024

Clinical Transplantation

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“…Previous studies have shown that miR-548a-3p is dysregulated in autoimmune diseases [ 17 – 19 ]. miR-548a-3p has been found to inhibit the proliferation and activation of macrophage-like (pTHP-1) cells by regulating the TLR4/NF-κB signaling pathway in rheumatoid arthritis [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, miR-548a-3p has been involved in keratinocyte proliferation by targeting PPP3R1 and T regulatory cells, pointing out a possible implication in the pathogenesis of psoriasis, a T cell-mediated autoimmune disease [ 18 ]. More recently, miR-548a-3p has been found to be significantly upregulated in acute graft-versus-host disease patients, suggesting its role as a potential noninvasive biomarkers in this disease [ 19 ]. However, our study is the first one to identify miR-548a-3p as treatment response biomarker in MS patients under fingolimod treatment.…”

Section: Discussionmentioning

confidence: 99%

“…However, according to our exploratory functional analysis, miR-548a-3p alone does not have a great effect on Treg number nor cytokine production through Akt2 expression, suggesting that miR-548a-3p main effect might be driven by regulation of these other targets (PIK3R1, PIK3R3 and PIK3CB), other cell types and/or by effect on other compartments such as the central nervous system which will need further attention. Previously reported roles of miRNA included in Validation cohort are shown in Additional file 2 : Table S2 [ 17 – 19 , 22 – 25 ].…”

Section: Discussionmentioning

confidence: 99%

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miRNA 548a-3p as biomarker of NEDA-3 at 2 years in multiple sclerosis patients treated with fingolimod

González-Martínez

Patel

Healy

et al. 2023

J Neuroinflammation

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Background Multiple sclerosis (MS) is a disabling autoimmune demyelinating disorder affecting young people and causing significant disability. In the last decade, different microRNA (miRNA) expression patterns have been associated to several treatment response therapies such as interferon and glatiramer acetate. Nowadays, there is increasing interest in the potential role of miRNA as treatment response biomarkers to the most recent oral and intravenous treatments. In this study, we aimed to evaluate serum miRNAs as biomarkers of No Evidence of Disease Activity (NEDA-3) at 2 years in patients with relapsing remitting MS (RRMS) treated with fingolimod. Main body A Discovery cohort of 31 RRMS patients treated with fingolimod were identified from the CLIMB study and classified as No Evidence of Disease Activity (NEDA-3) or Evidence of Disease Activity (EDA-3) after 2 years on treatment. Levels of miRNA expression were measured at 6 months using human serum miRNA panels and compared in EDA-3 and NEDA-3 groups using the Wilcoxon rank sum test. A set of differentially expressed miRNA was further validated in an independent cohort of 22 fingolimod-treated patients. We found that 548a-3p serum levels were higher levels in fingolimod-treated patients classified as NEDA-3, compared to the EDA-3 group in both the Discovery (n = 31; p = 0.04) and Validation (n = 22; p = 0.03) cohorts 6 months after treatment initiation; miR-548a-3p provided an AUC of 0.882 discriminating patients with NEDA-3 at 2 years in the Validation cohort. Conclusion Our results show differences in miR-548a-3p expression at 6 months after fingolimod start in patients with MS with NEDA-3 at 2 years. These results provide class III evidence of the use of miR-548a-3p as biomarker of NEDA-3 in patients with fingolimod.

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Noncoding RNAs in diagnosis and prognosis of graft‐versus‐host disease (GVHD)

Vajari

Moradinasab

Yousefi

et al. 2022

Journal Cellular Physiology

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Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is a functional therapy for a plethora of hematologic malignancies and immune disorders. Graft‐versus‐host disease (GVHD), on the other hand, is one of the major complications ahead of a successful HSCT, contributing to transplant‐associated morbidity and mortality. Notably, little is known about the underlying mechanism of this event; therefore, exploring precise biomarkers and uncovering the molecular pathogenesis of GVHD is valuable for early diagnosis and treatment optimization. Thanks to the advances in sequencing techniques, the noncoding sequences of the human genome—formerly considered "junk"—are now identified as functional molecules. Noncoding RNAs (ncRNA) control cellular responses by regulating gene expression, and previous studies have shown that these tiny molecules, especially microRNAs (miRNAs), can affect allogeneic T cell responses in both animal models and clinical experiments. The present study gives an overview of the functions of various miRNAs in regulating T cell responses in GVHD. We also provide an outlook on miRNAs and long noncoding RNAs (lncRNAs) potential role in GVHD with the hope of providing a future research direction for expanding their application as the sensitive and noninvasive diagnostic or prognostic biomarkers and also the promising therapeutic targets for improving outcomes after allogeneic HSCT.

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Circulating miR-455-3p, miR-5787, and miR-548a-3p as potential noninvasive biomarkers in the diagnosis of acute graft-versus-host disease: a validation study

Cited by 6 publications

References 57 publications

Diagnosis of Cutaneous Acute Graft‑Versus‑Host Disease Through Circulating Plasma miR‐638, miR‐6511b‐5p, miR‐3613‐5p, miR‐455‐3p, miR‐5787, and miR‐548a‐3p as Prospective Noninvasive Biomarkers Following Allogeneic Hematopoietic Stem Cell Transplantation

Diagnosis of Cutaneous Acute Graft‑Versus‑Host Disease Through Circulating Plasma miR‐638, miR‐6511b‐5p, miR‐3613‐5p, miR‐455‐3p, miR‐5787, and miR‐548a‐3p as Prospective Noninvasive Biomarkers Following Allogeneic Hematopoietic Stem Cell Transplantation

miRNA 548a-3p as biomarker of NEDA-3 at 2 years in multiple sclerosis patients treated with fingolimod

Noncoding RNAs in diagnosis and prognosis of graft‐versus‐host disease (GVHD)

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