Dataset Information

Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma.

ABSTRACT: BACKGROUND:Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein member of LGI family. We previously reported that LGI3 was expressed in brain, adipose tissues and skin, where it played roles as a multifunctional cytokine. We postulated that LGI3 may be involved in cytokine network in cancers. AIM:This study aimed to analyze differentially expressed genes in glioma tissues and glioma cohort data to investigate the prognostic role of LGI3 and its receptors. MATERIALS AND METHODS:Expression microarray data from Gene Expression Omnibus and glioma cohort data were analyzed using bioinformatic tools for statistical analysis, protein-protein interactions, functional enrichment and pathway analyses and prognostic association analysis. RESULTS:We found that LGI3 and its receptors, ADAM22 and ADAM23, were significantly downregulated in glioma tissues. Eleven upregulated genes and two downregulated genes in glioma tissues were found to be the previously reported LGI3-regulated genes. Protein-protein interaction network analysis showed that 85% of the LGI3-regulated and glioma-altered genes formed a cluster of interaction network. Functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed the association of these genes with hypoxia responses, p53 and Akt signaling and various cancer-related pathways including glioma. Analysis of expression microarray data of glioma cohorts demonstrated that low expression levels of LGI3, ADAM22 and ADAM23 were significantly associated with poor prognosis of glioma. CONCLUSION:These results propose that LGI3 and its receptors may play a prognostic role in glioma.

SUBMITTER: Kwon NS

PROVIDER: S-EPMC5449096 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma.

Kwon Nyoun Soo NS Kim Dong-Seok DS Yun Hye-Young HY

OncoTargets and therapy 20170524

<h4>Background</h4>Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein member of LGI family. We previously reported that LGI3 was expressed in brain, adipose tissues and skin, where it played roles as a multifunctional cytokine. We postulated that LGI3 may be involved in cytokine network in cancers.<h4>Aim</h4>This study aimed to analyze differentially expressed genes in glioma tissues and glioma cohort data to investigate the prognostic role of LGI3 and its receptors.<h4>Materials an ...[more]

PMID: 28579810

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Project description:LGI family member 3 (LGI3) is a member of the LGI protein family. In our previous studies, LGI3 was determined to be expressed in adipose tissues, skin and the brain, where it served as a pleiotropic cytokine. The results indicated that LGI3 levels are increased in adipose tissues of obese individuals in comparison with control individuals and that LGI3 suppressed adipogenesis via its receptor, disintegrin and metalloproteinase domain-containing protein 23. Additionally, it was reported that LGI3 upregulates tumor necrosis factor-α and downregulated adiponectin and hypothesized that LGI3 may act as a proinflammatory adipokine involved in adipose tissue inflammation. In the present study, cytokine arrays were used to analyze cytokine levels in adipose tissues and plasma of LGI3-knockout mice and signaling protein arrays used to analyze the expression and phosphorylation of these proteins in LGI3-treated preadipocytes. The results suggested that expression levels of 129 gene products (24 cytokines and 105 signaling proteins) were altered in response to LGI3 deficiency or LGI3 treatment, respectively. Protein-protein interaction network analysis of LGI3-regulated gene products revealed that 94% of the gene products (21 cytokines and 100 signaling proteins) formed an interaction network cluster. Functional enrichment analysis for the LGI3-regulated gene products, including those from our previous studies, revealed an association with numerous biological processes, including inflammatory responses, cellular differentiation and development and metabolic regulation. Gene co-expression network analysis revealed that these LGI3-regulated gene products were involved in various biological processes in an overlapping and differential manner between subcutaneous and visceral adipose tissues. Notably, inflammatory responses were more strongly associated with the LGI3-regulated gene co-expression network in visceral adipose tissues than in subcutaneous adipose tissues. Analysis of expression quantitative trait loci identified four single nucleotide variants that affect expression of LGI3 in an adipose depot-specific manner. Taken together, the results suggested that LGI3 may serve depot-specific roles as an adipokine in adipose tissues.

Project description:Leucine rich repeat LGI family member 3 (LGI3) is a member of the LGI protein family. Our previous studies reported that LGI3 was expressed in adipose tissues, brain and skin, where it served roles as a multifunctional cytokine and pro-inflammatory adipokine. It was hypothesized that LGI3 may be involved in cytokine networks in cancer. The present study aimed to analyze differentially expressed genes in non-small cell lung cancer (NSCLC) tissues and NSCLC cohort data, to evaluate the prognostic role of LGI3. Expression microarray and NSCLC cohort data were statistically analyzed by bioinformatic methods, and protein-protein interactions, functional enrichment and pathway, gene coexpression network (GCN) and prognostic association analyses were performed. The results demonstrated that the expression levels of LGI3 and its receptor a disintegrin and metalloproteinase domain-containing protein 22 were significantly decreased in NSCLC tissues. A total of two upregulated genes and 11 downregulated genes in NSCLC tissues were identified as LGI3-regulated genes. Protein-protein interaction network analysis demonstrated that all LGI3-regulated genes that were altered in NSCLC were involved in a protein-protein interaction network cluster. Functional enrichment, Kyoto Encyclopedia of Genes and Genomes pathway and GCN analyses demonstrated the association of these genes with the immune and inflammatory responses, angiogenesis, the tumor necrosis factor pathway, and chemokine and peroxisome proliferator-activated receptor signaling pathways. Analysis of NSCLC cohorts revealed that low expression levels of LGI3 was significantly associated with poor prognosis of NSCLC. Analysis of the somatic mutations of the LGI3 gene in NSCLC revealed that the amino acid residues altered in NSCLC included two single nucleotide polymorphism sites and three phylogenetically coevolved amino acid residues. Taken together, these results suggest that LGI3 may be a potential prognostic marker of NSCLC.

Project description:BackgroundAberrant DNA methylation occurs commonly during pathogenesis of neuroimmunological diseases and is of clinical value in various encephalitis subtypes. However, knowledge of the impact of DNA methylation changes on pathogenesis of leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis remains limited.MethodsA total of 44 cytokines and 10 immune checkpoint moleculars (ICMs) in the serum of patients with LGI1 encephalitis and healthy donors (HDs) were measured to evaluate the association of them with clinical parameters. Genome-wide DNA methylation profiles were performed in peripheral blood mononuclear cell (PBMC) from LGI1 encephalitis patients and HDs using reduced representation bisulfite sequencing (RRBS) and validated for the methylation status by pyrosequencing. MicroRNA profiles were acquired in serum exosome by small RNA sequencing. Targeted cytokines expression was assessed at the presence or absence of miR-2467-5p in PBMCs and the culture media, and the binding of miR-2467-5p and its targeted genes was validated by luciferase assay.ResultsThere existed significant difference in 22 cytokines/chemokines and 6 ICMs between LGI1 encephalitis patients and HDs. Decreased PDCD1 with increased ICAM1 could predict unfavorable prognosis in one-year follow-up for LGI1 encephalitis patients. Fifteen of cytokines/chemokines and ICMs presented DNA-methylated changes in the promoter and gene body using RRBS in which five were verified as methylation status by pyrosequencing, and the methylation level of CSF3, CCL2, and ICAM1 was conversely associated with their expression in PBMCs. By combining RRBS data with exosome-derived microRNA sequencing, we found that hypomethylated-driven hsa-miR-2467-5p presented elevated expression in serum exosomes and PBMCs in LGI1 encephalitis. Mechanically, miR-2467-5p significantly induced reduced expression of CSF3 and PDCD1 by binding with their 3`UTR while enhanced CCL15 expression, but not significantly correlated with peripheral blood CD19 + B cell proportion of LGI1 encephalitis patients.ConclusionsOur results provided convincing evidence for DNA methylation changes, microRNA profiles in serum exosome for LGI1 encephalitis, and we also identified several novel cytokines related to clinical features in which some represented epigenetic modification of methylated-driven pattern and microRNA modulation. Our study contributed to develop treatment for epigenetic pathogenesis in LGI1 encephalitis.

Project description:Background: Clinical presentations and treatment programs about anti-leucine-rich glioma inactivated 1 (LGI1) encephalitis still remain incompletely understood. Objective: This study analyzed the clinical features and therapeutic effects of anti-LGI1 encephalitis. Methods: PubMed, EMBASE, and the Cochrane Library were searched to identify published English and Chinese articles until April 2021. Data were extracted, analyzed, and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 80 publications detailing 485 subjects matched our inclusion criteria. Short-term memory loss (75.22%), faciobrachial dystonic seizures (FBDS) (52.53%), other seizures excluding FBDS (68.48%), psychiatric symptoms (57.67%), and sleep disturbances (34.30%) were the most frequently described symptoms in anti-LGI1 encephalitis. Hyponatremia (54.90%) was the most common hematologic examination change. The risk of incidence rate of malignant tumors was higher than in healthy people. The positive rate of anti-LGI1 in serum (99.79%) was higher than CSF (77.38%). Steroids (93.02%), IVIG (87.50%), and combined use (96.67%) all had a high remission rate in the initial visit. A total of 35 of 215 cases relapsed, of which 6/35 (17.14%) did not use first-line treatment, and 21 (60.00%) did not maintain long-term treatment. Plasma exchange (PE) could be combined in severe patients, immunosuppressant could be used for refractory patients or for recurrence and using an anti-epileptic drug to control seizures may benefit cognition. Conclusions: Short-term memory loss, FBDS, psychiatric symptoms, and hyponatremia were key features in identifying anti-LGI1 encephalitis. Serum and CSF antibody tests should be considered in diagnosis criteria. Steroids with IVIG should be recommended, PE was combined for use in severe patients, immunosuppressant therapy might improve outcomes if recurrence or progression occurred, and control seizures might benefit cognition. The useful ways to reduce relapse rate were early identification, clear diagnosis, rapid treatment, and maintaining long-term treatment. The follow-up advice was suggested according to the research of paraneoplastic syndrome, and concern about tumors was vital as well.

Dataset Information

Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma.

Publications

Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma.

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