A network-based approach reveals long non-coding RNAs associated with disease activity in lupus nephritis: key pathways for flare and potential biomarkers to be used as liquid biopsies

Sentis, George; Loukogiannaki, Catherine; Malissovas, Nikos; Nikolopoulos, Dionysis; Manolakou, Theodora; Flouda, Sofia; Grigoriou, Maria; Banos, Aggelos; Boumpas, Dimitrios T.; Filia, Anastasia

doi:10.3389/fimmu.2023.1203848

Cited by 4 publications

(1 citation statement)

References 71 publications

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“…In WGCNA, similarly expressed genes are clustered, their core genes are classified, and their correlation with sample characteristics (including clinicopathological indexes and treatment methods) is analyzed. With the assistance of WGCNA, the modules and genes related to the prognosis of diseases can be rapidly obtained from multiple transcriptomes, and the comparison of connectivity and genetic importance between modules can be performed [ 12 ]. Due to the fact that there is heterogeneity in nephroblastoma, the sensitivity and specificity of conventional differential expression in small samples are not high, and it is of little significance in clinical application.…”

Section: Introductionmentioning

confidence: 99%

Nephroblastoma-specific dysregulated gene SNHG15 with prognostic significance: scRNA-Seq with bulk RNA-Seq data and experimental validation

Chang,

Li,

et al. 2024

Discov Onc

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Wilms tumor (WT) is the most common malignancy of the genitourinary system in children. Currently, the Integration of single-cell RNA sequencing (scRNA-Seq) and Bulk RNA sequencing (RNA-Seq) analysis of heterogeneity between different cell types in pediatric WT tissues could more accurately find prognostic markers, but this is lacking. RNA-Seq and clinical data related to WT were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Small nucleolar RNA host gene 15 (SNHG15) was identified as a risk signature from the TARGET dataset by using weighted gene co-expression network analysis, differentially expressed analysis and univariate Cox analysis. After that, the functional mechanisms, immunological and molecular characterization of SNHG15 were investigated at the scRNA-seq, pan-cancer, and RNA-seq levels using Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), ESTIMATE, and CIBERSORT. Based on scRNA-seq data, we identified 20 clusters in WT and annotated 10 cell types. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing M2 macrophages as hubs for intercellular communication. In addition, in vitro cellular experiments showed that siRNAs interfering with SNHG15 significantly inhibited the proliferation and migration of G401 cells and promoted the apoptosis of G401 cells compared with the control group. The effect of siRNAs interfering with SNHG15 on EMT-related protein expression was verified by Western blotting assay. Thus, our findings will improve our current understanding of the pathogenesis of WT, and they are potentially valuable in providing novel prognosis markers for the treatment of WT.

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Section: Introductionmentioning

confidence: 99%

Nephroblastoma-specific dysregulated gene SNHG15 with prognostic significance: scRNA-Seq with bulk RNA-Seq data and experimental validation

Chang,

Li,

et al. 2024

Discov Onc

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Biomarkers for systemic lupus erythematosus: A scoping review

Zhang,

Xu,

Kang

2024

Immunity Inflam & Disease

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BackgroundIn recent years, newly discovered potential biomarkers have great research potential in the diagnosis, disease activity prediction, and treatment of systemic lupus erythematosus (SLE).ObjectiveIn this study, a scoping review of potential biomarkers for SLE over several years has identified the extent to which studies on biomarkers for SLE have been conducted, the specificity, sensitivity, and diagnostic value of potential biomarkers of SLE, the research potential of these biomarkers in disease diagnosis, and activity detection is discussed.MethodsIn PubMed and Google Scholar databases, “SLE,” “biomarkers,” “predictor,” “autoimmune diseases,” “lupus nephritis,” “neuropsychiatric SLE,” “diagnosis,” “monitoring,” and “disease activity” were used as keywords to systematically search for SLE molecular biomarkers published from 2020 to 2024. Analyze and summarize the literature that can guide the article.ConclusionsRecent findings suggest that some potential biomarkers may have clinical application prospects. However, to date, many of these biomarkers have not been subjected to repeated clinical validation. And no single biomarker has sufficient sensitivity and specificity for SLE. It is not scientific to choose only one or several biomarkers to judge the complex disease of SLE. It may be a good direction to carry out a meta‐analysis of various biomarkers to find SLE biomarkers suitable for clinical use, or to evaluate SLE by combining multiple biomarkers through mathematical models. At the same time, advanced computational methods are needed to analyze large data sets and discover new biomarkers, and strive to find biomarkers that are sensitive and specific enough to SLE and can be used in clinical practice, rather than only staying in experimental research and data analysis.

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Disentangling the riddle of systemic lupus erythematosus with antiphospholipid syndrome: blood transcriptome analysis reveals a less-pronounced IFN-signature and distinct molecular profiles in venous versus arterial events

Nikolopoulos,

Loukogiannaki,

Sentis

et al. 2024

Ann Rheum Dis

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IntroductionSystemic lupus erythematosus with antiphospholipid syndrome (SLE-APS) represents a challenging SLE endotype whose molecular basis remains unknown.MethodsWe analysed whole-blood RNA-sequencing data from 299 patients with SLE (108 SLE-antiphospholipid antibodies (aPL)-positive, including 67 SLE-APS; 191 SLE-aPL-negative) and 72 matched healthy controls (HC). Pathway enrichment analysis, unsupervised weighted gene coexpression network analysis and machine learning were applied to distinguish disease endotypes.ResultsPatients with SLE-APS demonstrated upregulated type I and II interferon (IFN) pathways compared with HC. Using a 100-gene random forests model, we achieved a cross-validated accuracy of 75.6% in distinguishing these two states. Additionally, the comparison between SLE-APS and SLE-aPL-negative revealed 227 differentially expressed genes, indicating downregulation of IFN-α and IFN-γ signatures, coupled with dysregulation of the complement cascade, B-cell activation and neutrophil degranulation. Unsupervised analysis of SLE transcriptome identified 21 gene modules, with SLE-APS strongly linked to upregulation of the ‘neutrophilic/myeloid’ module. Within SLE-APS, venous thromboses positively correlated with ‘neutrophilic/myeloid’ and ‘B cell’ modules, while arterial thromboses were associated with dysregulation of ‘DNA damage response (DDR)’ and ‘metabolism’ modules. Anticardiolipin and anti-β2GPI positivity—irrespective of APS status—were associated with the ‘neutrophilic/myeloid’ and ‘protein-binding’ module, respectively.ConclusionsThere is a hierarchical upregulation and—likely—dependence on IFN in SLE with the highest IFN signature observed in SLE-aPL-negative patients. Venous thrombotic events are associated with neutrophils and B cells while arterial events with DDR and impaired metabolism. This may account for their differential requirements for anticoagulation and provide rationale for the potential use of mTOR inhibitors such as sirolimus and the direct fIIa inhibitor dabigatran in SLE-APS.

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A network-based approach reveals long non-coding RNAs associated with disease activity in lupus nephritis: key pathways for flare and potential biomarkers to be used as liquid biopsies

Cited by 4 publications

References 71 publications

Nephroblastoma-specific dysregulated gene SNHG15 with prognostic significance: scRNA-Seq with bulk RNA-Seq data and experimental validation

Nephroblastoma-specific dysregulated gene SNHG15 with prognostic significance: scRNA-Seq with bulk RNA-Seq data and experimental validation

Biomarkers for systemic lupus erythematosus: A scoping review

Disentangling the riddle of systemic lupus erythematosus with antiphospholipid syndrome: blood transcriptome analysis reveals a less-pronounced IFN-signature and distinct molecular profiles in venous versus arterial events

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