Development and validation of plasma miRNA biomarker signature panel for the detection of early HIV-1 infection

Biswas, Santanu; Haleyurgirisetty, Mohan; Lee, Sherwin; Hewlett, Indira; Devadas, Krishnakumar

doi:10.1016/j.ebiom.2019.04.023

Cited by 70 publications

(52 citation statements)

References 42 publications

(51 reference statements)

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“…In addition, silencing miR-21 was found to be correlated with an increased clinical outcome [45]. In contrast with our results, miR-16 has been reported to be upregulated in individuals with cHL [43,46] and also with miR-223 in HIV-1 individuals compared to healthy controls [61]. We found that these overexpressed levels are higher in HIV-infected individuals who have not developed cHL, suggesting possible repression of their expression in HIV-associated cHL.…”

Section: Discussioncontrasting

confidence: 99%

Risk, Diagnostic and Predictor Factors for Classical Hodgkin Lymphoma in HIV-1-Infected Individuals: Role of Plasma Exosome-Derived miR-20a and miR-21

Hernández-Walias

Vázquez

Pacheco

et al. 2020

JCM

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The incidence of classical Hodgkin lymphoma (cHL) in the HIV-1 setting has increased 5–25-fold compared to that observed in the general population. This study aimed to determine whether selected micro RNAs (miRs) and other soluble biomarkers and cellular subsets are dysregulated in cHL and could be used as biomarkers. This was a retrospective and longitudinal matched case-control study of 111 Caucasian, HIV-1-infected adult individuals, including 37 individuals with cHL and 74 with no type of cancer. Immunovirological data, plasma exosome-derived miR-16, miR-20a, miR-21, miR-221, miR-223, miR-106a, miR-185, miR-23, miR-30d, miR-222, miR-146a and miR-324, plasma IL-6, sCD14, sCD27, sCD30, sIL-2R, TNFR1, and cell phenotyping of T and B lymphocytes and natural killer (NK) cells were analyzed. Before cHL diagnosis, miR-20a, miR-21, and sCD30 were higher in cHL (p = 0.008, p = 0.009 and p = 0.042, respectively), while miR-16 was down-regulated (p = 0.040). miR-20a and miR-21 were independently associated with cHL (p = 0.049 and p = 0.035, respectively). The combination of miR-20a and miR-21 showed a good AUC value of 0.832 with a moderate likelihood ratio positive (LR+) value of 5.6 and a slight likelihood ratio negative (LR−) value of 0.23. At cHL diagnosis, miR-20a, miR-21 and miR-324 were overexpressed in cHL (p = 0.005, p = 0.024, and p = 0.001, respectively), while miR-223, miR-16, miR-185 and miR-106a were down regulated (p = 0.042, p = 0.007, p = 0.006, and p = 0.002, respectively). In addition, sCD14, sCD27, sCD30 and IL2R levels were higher in these individuals (p = 0.038, p = 0.010, p = 0.030, p = 0.006, respectively). miR-20a was independently associated with cHL (p = 0.011). The diagnostic value of miR-20a showed good AUC value of 0.754 (p = 0.074) with a slight LR+ value of 2 and a slight LR− of 0.25. After chemotherapy, miR-20a was higher in those individuals who had an adverse outcome (p < 0.001), while sCD14 and sCD30 were higher (p < 0.001). A specific signature of miRs and cytokines associated with a subsequent cHL diagnosis was found in this study, especially miR-20a and miR-21. Also, another biomarker signature was found at cHL diagnosis, with a relevant discriminant disease value for miR-20a. Of note, miR-20a expression was higher in those individuals who had an adverse clinical outcome after chemotherapy.

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Section: Discussioncontrasting

confidence: 99%

Risk, Diagnostic and Predictor Factors for Classical Hodgkin Lymphoma in HIV-1-Infected Individuals: Role of Plasma Exosome-Derived miR-20a and miR-21

Hernández-Walias

Vázquez

Pacheco

et al. 2020

JCM

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“…Additionally, MiR-16-5p has been linked with the pathogenesis of several infectious diseases such as HIV-1 infection and malaria [105–107]. It is worth mentioning that miR-16-5p as a plasma diagnostic biomarker is able to distinguish severe and mild viral infections [108] and early HIV-1 infection from healthy individuals [106,109].…”

Section: Discussionmentioning

confidence: 99%

ACE2 interaction networks in COVID-19: a physiological framework for prediction of outcome in patients with cardiovascular risk factors

Wicik

Eyileten

Jakubik

et al. 2020

Preprint

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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019; is associated with adverse outcome in patients with cardiovascular disease (CVD).Aim: To characterize the interaction between SARS-CoV-2 and Angiotensin Converting Enzyme 2 (ACE2) functional networks with focus on CVD.Methods: Using bioinformatic tools, network medicine approaches and publicly available datasets, we investigated ACE2 tissue expression and described ACE2 interaction network which could be affected by SARS-CoV-2 infection. We identified top ACE2 interactors, including miRNAs which are shared regulators between the ACE2, virus-infection related proteins and heart interaction networks, using lung and nervous system networks as a reference. We also identified main SARS-CoV-2 risk groups and performed drug predictions for them.Results: We found the same range of ACE2 expression confidence in respiratory and cardiovascular systems (averaging 4.48 and 4.64, respectively). Analysing the complete ACE2 interaction network, we identified 11 genes (ACE2, DPP4, ANPEP, CCL2, TFRC, MEP1A, ADAM17, FABP2, NPC1, CLEC4M, TMPRSS2) associated with virus-infection related processes. Previously described genes associated with cardiovascular risk factors DPP4, CCL2 and ANPEP were extensively connected with top regulators of ACE2 network, including ACE, INS and KNG1. Enrichment analysis revealed several disease phenotypes associated with interaction networks of ACE2, heart tissue, and virus-infection related protein, with the strongest associations with the following diseases (in decreasing rank order): obesity, hypertensive disease, noninsulin dependent diabetes mellitus, congestive heart failure, and coronary artery disease. We described for the first time microRNAs-miR (miR-302c-5p, miR-1305, miR-587, miR-26b-5p, and mir-27a-3p), which were common regulators of the three networks: ACE2, heart tissue and virus-infection related proteins.Conclusion: Our study provides novel information regarding the complexity of signaling pathways affected by SARS-CoV-2 and proposes predictive tools as miR towards personalized diagnosis and therapy in COVID-19. Additionally, our study provides a list of miRNAs with biomarker potential in prediction of adverse outcome in patients with COVID-19 and CVD.

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“…MicroRNAs have been identified as potential biomarkers of infections caused by a range of pathogens, including Hendra virus (Stewart et al, 2013), HIV (Biswas et al, 2019), tuberculosis (Zhang et al, 2013), malaria (Li et al, 2018), including differentiating complicated and uncomplicated P. vivax malaria (Kaur et al, 2018) and Ebola (Duy et al, 2016). In some studies, changes in miRNA profiles were observed early in disease onset, before the pathogen could be directly detected and prior to the onset of seroconversion (Stewart et al, 2013;Biswas et al, 2019). MicroRNAs have also been implicated in influenza infections (Scheller et al, 2019) and rhinoviruses (Hasegawa et al, 2018).…”

Section: The Potential For Mirnas To Improve Disease Outcomesmentioning

confidence: 99%

“…These miRNAs may be purely markers of viral exposure or may play a key role in HIV resistance. Recently, a panel of four miRNAs (miR-16-5p, -20b-5p, -195-5p, and -223-3p) was developed and tested for HIV diagnostic utility (Biswas et al, 2019). Blind testing was able to identify all positive samples and healthy controls with 100% sensitivity and specificity.…”

Section: Advantages Of Mirna Biomarkers I: Early Detectionmentioning

confidence: 99%

MicroRNA Biomarkers for Infectious Diseases: From Basic Research to Biosensing

et al. 2020

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In the pursuit of improved diagnostic tests for infectious diseases, several classes of molecules have been scrutinized as prospective biomarkers. Small (18-22 nucleotide), non-coding RNA transcripts called microRNAs (miRNAs) have emerged as promising candidates with extensive diagnostic potential, due to their role in numerous diseases, previously established methods for quantitation and their stability within biofluids. Despite efforts to identify, characterize and apply miRNA signatures as diagnostic markers in a range of non-infectious diseases, their application in infectious disease has advanced relatively slowly. Here, we outline the benefits that miRNA biomarkers offer to the diagnosis, management, and treatment of infectious diseases. Investigation of these novel biomarkers could advance the use of personalized medicine in infectious disease treatment, which raises important considerations for validating their use as diagnostic or prognostic markers. Finally, we discuss new and emerging miRNA detection platforms, with a focus on rapid, point-of-care testing, to evaluate the benefits and obstacles of miRNA biomarkers for infectious disease.

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Development and validation of plasma miRNA biomarker signature panel for the detection of early HIV-1 infection

Cited by 70 publications

References 42 publications

Risk, Diagnostic and Predictor Factors for Classical Hodgkin Lymphoma in HIV-1-Infected Individuals: Role of Plasma Exosome-Derived miR-20a and miR-21

Risk, Diagnostic and Predictor Factors for Classical Hodgkin Lymphoma in HIV-1-Infected Individuals: Role of Plasma Exosome-Derived miR-20a and miR-21

ACE2 interaction networks in COVID-19: a physiological framework for prediction of outcome in patients with cardiovascular risk factors

MicroRNA Biomarkers for Infectious Diseases: From Basic Research to Biosensing

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