scholarly journals Identification of a ferroptosis-related gene pair biomarker with immune infiltration landscapes in ischemic stroke: a bioinformatics-based comprehensive study

BMC Genomics ◽  
2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Jiaxin Fan ◽  
Mengying Chen ◽  
Shuai Cao ◽  
Qingling Yao ◽  
Xiaodong Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Gene Pair ◽  
Plasma Cells ◽  
Single Gene ◽  
Machine Learning Algorithms ◽  
Related Gene ◽  
Immune Infiltration ◽  
Cerna Network ◽  
Competitive Endogenous Rna

Abstract Background Ischemic stroke (IS) is a principal contributor to long-term disability in adults. A new cell death mediated by iron is ferroptosis, characterized by lethal aggregation of lipid peroxidation. However, a paucity of ferroptosis-related biomarkers early identify IS until now. This study investigated potential ferroptosis-related gene pair biomarkers in IS and explored their roles in immune infiltration. Results In total, we identified 6 differentially expressed ferroptosis-related genes (DEFRGs) in the metadata cohort. Of these genes, 4 DEFRGs were incorporated into the competitive endogenous RNA (ceRNA) network, including 78 lncRNA-miRNA and 16 miRNA-mRNA interactions. Based on relative expression values of DEFRGs, we constructed gene pairs. An integrated scheme consisting of machine learning algorithms, ceRNA network, and gene pair was proposed to screen the key DEFRG biomarkers. The receiver operating characteristic (ROC) curve witnessed that the diagnostic performance of DEFRG pair CDKN1A/JUN was superior to that of single gene. Moreover, the CIBERSORT algorithm exhibited immune infiltration landscapes: plasma cells, resting NK cells, and resting mast cells infiltrated less in IS samples than controls. Spearman correlation analysis confirmed a significant correlation between plasma cells and CDKN1A/JUN (CDKN1A: r = − 0.503, P < 0.001, JUN: r = − 0.330, P = 0.025). Conclusions Our findings suggested that CDKN1A/JUN could be a robust and promising gene-pair diagnostic biomarker for IS, regulating ferroptosis during IS progression via C9orf106/C9orf139-miR-22-3p-CDKN1A and GAS5-miR-139-5p/miR-429-JUN axes. Meanwhile, plasma cells might exert a vital interplay in IS immune microenvironment, providing an innovative insight for IS therapeutic target.

Identification of a Metabolism-Related Risk Signature to Predict the Outcome and Immune Infiltration of Esophageal Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Yu Liu ◽  
Liyu Wang ◽  
Hengchang Liu ◽  
He Tian ◽  
Tao Fan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Plasma Cells ◽  
Immune Cell ◽  
Gene Signature ◽  
Metabolic Reprogramming ◽  
Immune Cell Infiltration ◽  
Related Gene ◽  
Prognostic Signature ◽  
Immune Infiltration

Abstract Background: Metabolic reprogramming is associated with tumor heterogeneity and progression. Understanding the characteristics of metabolic reprogramming in esophageal squamous cell carcinoma (ESCC) might help us to uncover new biomarkers for patient outcomes and targets for therapies.Methods: In this study, metabolism-related genes were screened from mRNA microarray data (GSE53624, GSE53622). Consensus clustering analysis was used to divide tumors into subgroups. Survival analysis and univariate Cox analysis were performed to select prognostic genes. A metabolism-related gene signature was established with multivariate Cox proportional hazards regression (PHR) analysis in the training group (GSE53624). Gene set enrichment analysis (GSEA) and CIBERSORT were used to analyze functional enrichment and immune cell infiltration.The gene signature and immune infiltration were verified in two public databases (GSE53622, TCGA-ESCC) and in two independent cohorts, 95 and 119 ESCC patients, by immunohistochemistry (IHC) analysis. Results: Based on prognosis-related metabolic gene expression, three cluster subgroups (k = 3) were identified with significantly different immune cell infiltration patterns, clinical features and overall survival (OS) times. Then, we developed a multigene (INPP5E, CD38 and POLR3G) prognostic signature that showed better predictive ability and was found to be an independent prognostic risk factor in ESCC database and two public database analyses. This result could also be verified by multicenter IHC experiment and indicated the clinical application potential. In addition, GSEA showed that several tumor-related pathways were associated with the prognostic signature. Furthermore, the immune cell infiltration of regulatory T cells (Tregs) and plasma cells displayed an obvious correlation with prognostic signature and IHC experiment in 119 cohort also support this result.Conclusions: Our study indicated that the metabolism-related prognostic gene could stratify patients into subgroups and was associated with immune infiltration, clinical features and outcomes. The three-gene prognostic signature from metabolic-related gene displays a good ability to predict OS and the infiltration of immunosuppressive Tregs and plasma cells.

scholarly journals Identification the Synergistic Effect of Immune-Related lncRNA KIAA0125 and Vitamin D Metabolism Related Gene CYP24A1 in Periodontitis

2020 ◽  
Author(s):  
Yang Li ◽  
Ruixue Li ◽  
Ying Wu ◽  
Chan-Juan Gong ◽  
XiaoJun Ding
Keyword(s):  
Vitamin D ◽  
Plasma Cells ◽  
Alveolar Bone ◽  
Metabolic Enzyme ◽  
Periodontal Ligament Cells ◽  
Related Gene ◽  
Vitamin D Metabolism ◽  
Cerna Network ◽  
Transcriptomic Sequencing

Abstract Background: Periodontitis is a chronic infectious disease characterized by gingival inflammation and progressive destruction of alveolar bone. The interaction of periodontal plaque microorganisms and host immune response affects the process and progression of periodontitis. However, the specific mechanisms and biomarkers involved in periodontitis remain to be further studied. Methods: In the present research, we explored the expression profile data of differentially expressed lncRNAs and immune-related mRNAs and constructed the competing endogenous RNAs (ceRNA) network. The CIBERSORT analysis was used to infer the composition of 22 immune cells in periodontitis. The genes in ceRNA network were further screened by weighted gene co-expression network analysis (WGCNA), transcriptomic sequencing and PCR. Results: Our results indicated that a total of 1 lncRNA (KIAA0125), 3 miRNAs (miR-449c-5p, miR-125a-5p and miR-125b-5p) and 2 mRNAs (CYP24A1, BTG2) were involved in establishing the ceRNA network for periodontitis. The expression of KIAA0125 was highly correlated with plasma cells and B cells markers. The WGCNA and transcriptomic sequencing screened out the key gene as the vitamin D metabolic enzyme CYP24A1. The experimental results showed both KIAA0125 and CYP24A1 were highly expressed in the periodontitis gingival tissues. In vitro experiments, the expression of KIAA0125 in human periodontal ligament cells (hPDLCs) were increased after the treatment of lipopolysaccharide and 1,25-dihydroxyvitamin D3 (1,25D) (P < 0.05). In addition, we found that 1,25D could alleviate the inflammation of LPS-induced hPDLCs, while the increased expression of KIAA0125 and CYP24A1 would antagonize the anti-inflammatory effect. Conclusion: In conclusion, immune-related lncRNA KIAA0125 and vitamin D metabolism related gene CYP24A1 can be used as potential diagnostic indicators of periodontitis.

scholarly journals Tumor Mutation Burden-Associated LINC00638/miR-4732-3p/ULBP1 Axis Promotes Immune Escape via PD-L1 in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Feng Qi ◽  
Xiaojing Du ◽  
Zhiying Zhao ◽  
Ding Zhang ◽  
Mengli Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Model ◽  
Immune Escape ◽  
Prognostic Score ◽  
Machine Learning Algorithms ◽  
Luciferase Reporter ◽  
Tumor Mutation Burden ◽  
Immune Infiltration ◽  
Cerna Network ◽  
Mutation Burden

Tumor mutation burden (TMB) is associated with immune infiltration, while its underlying mechanism in hepatocellular carcinoma (HCC) remains unclear. A long noncoding RNA (lncRNA)-related competitive endogenous RNA (ceRNA) network can regulate various tumor behaviors, and research about its correlation with TMB and immune infiltration is warranted. Data were downloaded from TCGA and ArrayExpress databases. Cox analysis and machine learning algorithms were employed to establish a lncRNA-based prognostic model for HCC. We then developed a nomogram model to predict overall survival and odds of death for HCC patients. The association of this prognostic model with TMB and immune infiltration was also analyzed. In addition, a ceRNA network was constructed by using DIANA-LncBasev2 and the starBase database and verified by luciferase reporter and colocalization analysis. Multiplex immunofluorescence was applied to determine the correlation between ULBP1 and PD-L1. An eight-lncRNA (SLC25A30-AS1, HPN-AS1, LINC00607, USP2-AS1, HCG20, LINC00638, MKLN1-AS and LINC00652) prognostic score model was constructed for HCC, which was highly associated with TMB and immune infiltration. Next, we constructed a ceRNA network, LINC00638/miR-4732-3p/ULBP1, that may be responsible for NK cell infiltration in HCC with high TMB. However, patients with high ULBP1 possessed a poorer prognosis. Using multiplex immunofluorescence, we found a significant correlation between ULBP1 and PD-L1 in HCC, and patients with high ULBP1 and PD-L1 had the worst prognosis. In brief, the eight-lncRNA model is a reliable tool to predict the prognosis of HCC patients. The LINC00638/miR-4732-3p/ULBP1 axis may regulate immune escape via PD-L1 in HCC with high TMB.

Long-Term Brain Atrophy after Focal Ischemic Stroke: A Longitudinal Study Applying Deformation-Based Morphometry

2004 ◽  
Vol 35 (03) ◽  
Author(s):  
S Schnaudigel ◽  
T Ugur ◽  
F Kruggel ◽  
HJ Mentzel ◽  
C Fitzek ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Longitudinal Study ◽  
Brain Atrophy ◽  
Deformation Based Morphometry

Mechanical thrombectomy in pediatric stroke: systematic review, individual patient data meta-analysis, and case series

2019 ◽  
Vol 24 (5) ◽  
pp. 558-571 ◽  
Author(s):  
Kartik Bhatia ◽  
Hans Kortman ◽  
Christopher Blair ◽  
Geoffrey Parker ◽  
David Brunacci ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Case Reports ◽  
Meta Analysis ◽  
Case Series ◽  
Neurological Outcomes

OBJECTIVEThe role of mechanical thrombectomy in pediatric acute ischemic stroke is uncertain, despite extensive evidence of benefit in adults. The existing literature consists of several recent small single-arm cohort studies, as well as multiple prior small case series and case reports. Published reports of pediatric cases have increased markedly since 2015, after the publication of the positive trials in adults. The recent AHA/ASA Scientific Statement on this issue was informed predominantly by pre-2015 case reports and identified several knowledge gaps, including how young a child may undergo thrombectomy. A repeat systematic review and meta-analysis is warranted to help guide therapeutic decisions and address gaps in knowledge.METHODSUsing PRISMA-IPD guidelines, the authors performed a systematic review of the literature from 1999 to April 2019 and individual patient data meta-analysis, with 2 independent reviewers. An additional series of 3 cases in adolescent males from one of the authors’ centers was also included. The primary outcomes were the rate of good long-term (mRS score 0–2 at final follow-up) and short-term (reduction in NIHSS score by ≥ 8 points or NIHSS score 0–1 at up to 24 hours post-thrombectomy) neurological outcomes following mechanical thrombectomy for acute ischemic stroke in patients < 18 years of age. The secondary outcome was the rate of successful angiographic recanalization (mTICI score 2b/3).RESULTSThe authors’ review yielded 113 cases of mechanical thrombectomy in 110 pediatric patients. Although complete follow-up data are not available for all patients, 87 of 96 (90.6%) had good long-term neurological outcomes (mRS score 0–2), 55 of 79 (69.6%) had good short-term neurological outcomes, and 86 of 98 (87.8%) had successful angiographic recanalization (mTICI score 2b/3). Death occurred in 2 patients and symptomatic intracranial hemorrhage in 1 patient. Sixteen published thrombectomy cases were identified in children < 5 years of age.CONCLUSIONSMechanical thrombectomy may be considered for acute ischemic stroke due to large vessel occlusion (ICA terminus, M1, basilar artery) in patients aged 1–18 years (Level C evidence; Class IIb recommendation). The existing evidence base is likely affected by selection and publication bias. A prospective multinational registry is recommended as the next investigative step.

scholarly journals EGFR-mutant NSCLC presenting with stroke and massive systemic embolization as the first manifestation: case report

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zheng Wang ◽  
Jiangyong Miao ◽  
Lina Wang ◽  
Ying Liu ◽  
Hui Ji ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Cancer Therapy ◽  
Acute Ischemic Stroke ◽  
Oral Anticoagulants ◽  
Initial Manifestation ◽  
Arterial Thromboembolism ◽  
Systemic Embolization ◽  
Effective Cancer Therapy

Abstract Background Presentation with massive systemic embolization as the initial manifestation of occult malignancy is infrequent. The standard management of cancer-related arterial thromboembolism has not yet been established. Case presentation We described a case of Trousseau’s syndrome resulting in acute ischemic stroke concomitant with multiple embolizations in the spleen and kidney during oral administration of dabigatran for pulmonary embolism preceding the diagnosis of a malignant tumor. A cancer-related hypercoagulable state was suspected because the patient was admitted to the neurology department due to acute ischemic stroke with three territory infarcts on diffusion-weighted imaging (DWI) in the absence of identifiable conventional risk factors and brain vessel narrowing. The patient was subsequently diagnosed with epidermal growth factor receptor (EGFR) mutation–positive non-small-cell lung cancer (NSCLC) (stage IV) with pleural metastasis. Administration of low-molecular-weight heparin followed by long-term dabigatran under effective cancer therapy comprising gefitinib and subsequent chemotherapy did not cause stroke relapse during the 1-year follow-up. Conclusions This case suggests that cancer-related hypercoagulability should be considered an important etiology for stroke patients who develop unexplained disseminated acute cerebral infarction without conventional stroke risk factors, especially concomitant with multiple organ embolization. Novel oral anticoagulants may be an alternative therapy for the long-term management of cancer-related arterial thromboembolism under effective cancer therapy.

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