scholarly journals Bioinformatics method combined with logistic regression analysis reveal potentially important miRNAs in ischemic stroke

2020 ◽  
Vol 40 (8) ◽  
Author(s):  
Zhiqiang Wei ◽  
Xingdi Qi ◽  
Yan Chen ◽  
Xiaoshuang Xia ◽  
Boyu Zheng ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Ischemic Stroke ◽  
Logistic Regression Analysis ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Bioconductor Package ◽  
Diagnostic Signature

Abstract Purpose: The present study aimed to investigate the comprehensive differential expression profile of microRNAs (miRNAs) by screening for miRNA expression in ischemic stroke and normal samples. Methods: Differentially expressed miRNA (DEM) analysis was conducted using limma R Bioconductor package. Target genes of DEMs were identified from TargetScanHuman and miRTarBase databases. Functional enrichment analysis of the target genes was performed using clusterProfiler R Bioconductor package. The miRNA-based ischemic stroke diagnostic signature was constructed via logistic regression analysis. Results: Compared with the normal cohort, a total of 14 DEMs, including 5 up-regulated miRNAs and 9 down-regulated miRNAs, were identified in ischemic stroke patients. These DEMs have 1600 regulatory targets. Using a logistic regression model, the top five miRNAs were screened for constructing an miRNA-based ischemic stroke diagnostic signature. Using the miRNA–mRNA interaction pairs, two target genes (specificity protein 1 (SP1) and Argonaute 1 (AGO1)) were speculated to be the primary genes of ischemic stroke. Discussion and conclusion: Here, several potential miRNAs biomarkers were identified and an miRNA-based diagnostic signature for ischemic stroke was established, which can be a valuable reference for future clinical researches.

scholarly journals Construction and Validation of a Nomogram for the Preoperative Prediction of Lymph Node Metastasis in Gastric Cancer

2021 ◽  
Vol 28 ◽  
pp. 107327482110271
Author(s):  
Shilong Li ◽  
Zongxian Zhao ◽  
Huaxiang Yang ◽  
Daohan Wang ◽  
Weilin Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Lymph Node ◽  
Risk Group ◽  
Enrichment Analysis ◽  
Roc Curves ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Node Metastasis

Background: Increasing evidence indicated that the tumor microenvironment (TME) plays a critical role in tumor progression. This study aimed to identify and evaluate mRNA signature involved in lymph node metastasis (LNM) in TME for gastric cancer (GC). Methods: Gene expression and clinical data were downloaded from The Cancer Genome Atlas (TCGA). The ESTIMATE algorithm was used to evaluate the TME of GC. The heatmap and Venn plots were applied for visualizing and screening out intersect differentially expressed genes (DEGs) involved in LNM in TME. Functional enrichment analysis, gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network were also conducted. Furthermore, binary logistic regression analysis were employed to develop a 4-mRNAs signature for the LNM prediction. ROC curves were applied to validate the LNM predictive ability of the riskscore. Nomogram was constructed and calibration curve was plotted to verify the predictive power of nomogram. Results: A total of 88 LNM related DEGs were identified. Functional enrichment analysis and GSEA implied that those genes were associated with some biological processes, such as ion transportation, lipid metabolism and thiolester hydrolase activity. After univariate and multivariate logistic regression analysis, 4 mRNAs (RASSF2, MS4A2, ANKRD33B and ADH1B) were eventually screened out to develop a predictive model. ROC curves manifested the good performance of the 4-mRNAs signature. The proportion of patients with LNM in high-risk group was significantly higher than that in low-risk group. The C-index of nomogram from training and test cohorts were 0.865 and 0.765, and the nomogram was well calibrated. Conclusions: In general, we identified a 4-mRNAs signature that effectively predicted LNM in GC patients. Moreover, the 4-mRNAs signature and nomogram provide a guidance for the preoperative evaluation and postoperative treatment of GC patients.

scholarly journals A Two-Gene-Based Diagnostic Signature for Ruptured Intracranial Aneurysms

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuwang Li ◽  
Jie Qin
Keyword(s):  
Gene Expression ◽  
Risk Assessment ◽  
Logistic Regression ◽  
Logistic Regression Model ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Bioconductor Package ◽  
Key Genes

Background: Ruptured intracranial aneurysm (IA) is a disease with high mortality. Despite the great progress in treating ruptured IA, methods for risk assessment of ruptured IA remain limited.Methods: In this study, we aim to develop a robust diagnostic model for ruptured IA. Gene expression profiles in blood samples of 18 healthy persons and 43 ruptured IA patients were obtained from the Gene Expression Omnibus (GEO). Differential expression analysis was performed using limma Bioconductor package followed by functional enrichment analysis via clusterProfiler Bioconductor package. Immune cell compositions in ruptured IA and healthy samples were assessed through the CIBERSORT tool. Protein–protein interaction (PPI) was predicted based on the STRING database. Logistic regression model was used for the construction of predictive model for distinguishing ruptured IA and healthy samples. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to validate the gene expression between the ruptured IA and healthy samples.Results: A total of 58 differentially expressed genes (DEGs) were obtained for ruptured IA patients compared with healthy controls. Functional enrichment analysis showed that the DEGs were enriched in biological processes related to neutrophil activation, neutrophil degranulation, and cytokine–cytokine receptor interaction. Notably, immune analysis results proved that the rupture of IA might be related to immune cell distribution. We further identified 24 key genes as hub genes using the PPI networks. The logistic regression model trained based on the 24 key genes ultimately retained two genes, i.e., IL2RB and CCR7, which had great potential for risk assessment for rupture of IA. The RT-qPCR further validated that compared with the healthy samples, the expression levels of IL2RB and CCR7 were decreased in ruptured IA samples.Conclusions: This study might be helpful for cohorts who have a high risk of ruptured IA for early diagnosis and prevention of the disease.

scholarly journals Identification of Tumorigenic and Prognostic Biomarkers in Colorectal Cancer Based on microRNA Expression Profiles

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuntao Shi ◽  
Yingying Zhuang ◽  
Jialing Zhang ◽  
Mengxue Chen ◽  
Shangnong Wu
Keyword(s):  
Target Genes ◽  
Cox Regression ◽  
Expression Profiles ◽  
Survival Rates ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Risk Groups ◽  
Normal Mucosa ◽  
Microrna Expression ◽  
Functional Enrichment

Objective. Although noncoding RNAs, especially the microRNAs, have been found to play key roles in CRC development in intestinal tissue, the specific mechanism of these microRNAs has not been fully understood. Methods. GEO and TCGA database were used to explore the microRNA expression profiles of normal mucosa, adenoma, and carcinoma. And the differential expression genes were selected. Computationally, we built the SVM model and multivariable Cox regression model to evaluate the performance of tumorigenic microRNAs in discriminating the adenomas from normal tissues and risk prediction. Results. In this study, we identified 20 miRNA biomarkers dysregulated in the colon adenomas. The functional enrichment analysis showed that MAPK activity and MAPK cascade were highly enriched by these tumorigenic microRNAs. We also investigated the target genes of the tumorigenic microRNAs. Eleven genes, including PIGF, TPI1, KLF4, RARS, PCBP2, EIF5A, HK2, RAVER2, HMGN1, MAPK6, and NDUFA2, were identified to be frequently targeted by the tumorigenic microRNAs. The high AUC value and distinct overall survival rates between the two risk groups suggested that these tumorigenic microRNAs had the potential of diagnostic and prognostic value in CRC. Conclusions. The present study revealed possible mechanisms and pathways that may contribute to tumorigenesis of CRC, which could not only be used as CRC early detection biomarkers, but also be useful for tumorigenesis mechanism studies.

scholarly journals miRNA Mediated Noise Making of 3′UTR Mutations in Cancer

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 545 ◽  
Author(s):  
Wei Wu ◽  
Lingxiang Wu ◽  
Mengyan Zhu ◽  
Ziyu Wang ◽  
Min Wu ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Target Genes ◽  
Expression Profiles ◽  
Tumor Development ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Messenger Rnas ◽  
Cellular Functions ◽  
Mrna Binding

Somatic mutations in 3′-untranslated regions (3′UTR) do not alter amino acids and are considered to be silent in cancers. We found that such mutations can promote tumor progression by altering microRNA (miRNA) targeting efficiency and consequently affecting miRNA–mRNA interactions. We identified 67,159 somatic mutations located in the 3′UTRs of messenger RNAs (mRNAs) which can alter miRNA–mRNA interactions (functional somatic mutations, funcMutations), and 69.3% of these funcMutations (the degree of energy change > 12 kcal/mol) were identified to significantly promote loss of miRNA-mRNA binding. By integrating mRNA expression profiles of 21 cancer types, we found that the expression of target genes was positively correlated with the loss of absolute affinity level and negatively correlated with the gain of absolute affinity level. Functional enrichment analysis revealed that genes carrying funcMutations were significantly enriched in the MAPK and WNT signaling pathways, and analysis of regulatory modules identified eighteen miRNA modules involved with similar cellular functions. Our findings elucidate a complex relationship between miRNA, mRNA, and mutations, and suggest that 3′UTR mutations may play an important role in tumor development.

Abstract TP21: Is Presence of Diabetes Mellitus a Key Prognostic Factor among Patients Receiving Endovascular Treatment for Acute Ischemic Stroke?

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Seong-Joon Lee ◽  
Yang-Ha Hwang ◽  
Ji Man Hong ◽  
Jin Wook Choi ◽  
Dong-Hun Kang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Logistic Regression Analysis ◽  
Multiple Logistic Regression Analysis ◽  
Univariate Analysis ◽  
Intravenous Thrombolysis ◽  
The Impact

Introduction: Given the recent positive endovascular therapy trials for acute ischemic stroke (AIS), this therapeutic strategy is now being increasingly incorporated into routine clinical practice. Identifying prognostic factors among AIS patients receiving endovascular revascularization treatments (ERT) in the real world could be important for clinicians and patients. While the impact of diabetes mellitus (DM) on IV thrombolytic outcomes after AIS has been extensively investigated, there is a paucity of data assessing effects of DM on ERT outcomes after AIS. We evaluated the impact of comorbid DM on ERT for AIS. Methods: From Jan 2011 to Feb 2016, patients with AIS who underwent ERT for cervicocephalic occlusions were consecutively enrolled into the Acute Stroke due to Intracranial Atherosclerotic occlusion and Neurointervention - Korean Retrospective (ASIAN KR) registry from 3 hospitals. Patients were excluded if onset to puncture time over 8 hours, in-hospital stroke, or unavailable 3-month mRS. DM was diagnosed if a patient had the history, or hemoglobin A1c on admission was over 6.5. Univariate analysis was performed to compare the characteristics between DM and non-DM population. Multiple logistic regression analysis was used to validate the effect of comorbid DM on 3 month outcomes. Results: Of 721 patients, 667 (93%) were finally included, with 233 DM patients and 434 non-DM patients. In the univariate analysis, comorbidity with hypertension (71.2% vs. 58.3%, p=0.001) and dyslipidemia (36.7% vs. 26.7%, p=0.012) were more frequent in the DM population. Periprocedural factors such as target vessels, intravenous thrombolysis, and final reperfusion grades did not differ. Good outcomes with mRS 0-2 were less frequent in the DM population (43.3% vs. 53.7%, p=0.011). In the logistic regression analysis adjusting age, male sex, initial NIHSS, premorbid mRS, hypertension history, atrial fibrillation, intravenous thrombolysis, onset to puncture time and successful reperfusion, DM was an independent predictor of poor outcomes (mRS 3-6; 1.933, 1.274-2.933, p=0.002). Conclusion: In patients receiving ERT for AIS due to cervicocephalic artery occlusions, the presence of DM as a comorbidity confers greater odds of a poor functional outcome.

scholarly journals 3131 ONCOSTREAMS: NOVEL DYNAMICS PATHOLOGICAL MULTICELLULAR STRUCTURES INVOLVED IN GLIOBLATOMA GROWTH AND INVASION

2019 ◽  
Vol 3 (s1) ◽  
pp. 111-111 ◽  
Author(s):  
Andrea Comba ◽  
Patrick Dunn ◽  
Anna E Argento ◽  
Padma Kadiyala ◽  
Sebastien Motsch ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Target Genes ◽  
Collective Motion ◽  
Malignant Tumors ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Genetically Engineered ◽  
Functional Enrichment ◽  
Low Grade ◽  
Normal Brain

OBJECTIVES/SPECIFIC AIMS: Oncostreams represent a novel growth pattern of GBM. In this study we uncovered the cellular and molecular mechanism that regulates the oncostreams function in GBM growth and invasion. METHODS/STUDY POPULATION: We studied oncostreams organization and function using genetically engineered mouse gliomas models (GEMM), mouse primary patient derived GBM model and human glioma biopsies. We evaluated the molecular landscape of oncostreams by laser capture microdissection (LCM) followed by RNA-Sequencing and bioinformatics analysis. RESULTS/ANTICIPATED RESULTS: Oncostreams are multicellular structures of 10-20 cells wide and 2-400 μm long. They are distributed throughout the tumors in mouse and human GBM. Oncostreams are heterogeneous structures positive for GFAP, Nestin, Olig2 and Iba1 cells and negative for Neurofilament. Using GEMM we found a negative correlation between oncostream density and animal survival. Moreover, examination of patient’s glioma biopsies evidenced that oncostreams are present in high grade but no in low grade gliomas. This suggests that oncostreams may play a role in tumor malignancy. Our data also indicated that oncostreams aid local invasion of normal brain. Transcriptome analysis of oncostreams revealed 43 differentially expressed (DE) genes. Functional enrichment analysis of DE genes showed that “collagen catabolic processes”, “positive regulation of cell migration”, and “extracellular matrix organization” were the most over-represented GO biological process. Network analysis indicated that Col1a1, ACTA2, MMP9 and MMP10 are primary target genes. These genes were also overexpressed in more malignant tumors (WT-IDH) compared to the less malignant (IDH1- R132H) tumors. Confocal time lapse imagining of 3D tumor slices demonstrated that oncostreams display a collective motion pattern within gliomas that has not been seen before. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, oncostreams are anatomically and molecularly distinctive, regulate glioma growth and invasion, display collective motion and are regulated by the extracellular matrix. We propose oncostreams as novel pathological markers valuable for diagnosis, prognosis and designing therapeutics for GBM patients.

scholarly journals Downregulation of miRNA-205 Expression and Biological Mechanism in Prostate Cancer Tumorigenesis and Bone Metastasis

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Yu Sun ◽  
Sheng-Hua Li ◽  
Ji-Wen Cheng ◽  
Gang Chen ◽  
Zhi-Guang Huang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Protein Level ◽  
Target Genes ◽  
Mrna Level ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Forest Plot ◽  
Biological Mechanism

Background. The expression and mechanism of microRNA-205 (miRNA-205) in prostate cancer (PCa) and its bone metastasis remain controversial. Materials and Methods. The expression and discriminating capability of miRNA-205 were assessed by drawing a forest plot and a summarized receiver operating characteristic (SROC) curve, using data available from 27 miRNA-array and miRNA-sequencing datasets. The miRNA-205 target genes were acquired from online prediction tools, differentially upregulated genes in PCa, and differentially expressed genes (DEGs) after miRNA-205 transfection into PCa cell lines. Functional enrichment analysis was conducted to explore the biological mechanism of miRNA-205 targets. Immunohistochemistry (IHC) was applied to verify the protein level of the hub gene. Results. The expression of miRNA-205 in the PCa group (1,461 samples) was significantly lower than that in the noncancer group (510 samples), and the downregulation of miRNA-205 showed excellent sensitivity and specificity in differentiating between the two groups. In bone metastatic PCa, the miRNA-205 level was further reduced than in nonbone metastatic PCa, and it showed a good capability in distinguishing between the two groups. In total, 153 miRNA-205 targets were screened through the three aforementioned methods. Based on the results of functional enrichment analysis, the targets of miRNA-205 were mainly enriched during chromosome segregation and phospholipid-translocating ATPase activity and in the spindle microtubule and the p53 signaling pathway. CDK1 had the highest connectivity in the PPI network analysis and was screened as one of the hub genes. A statistically significant negative correlation between miRNA-205 and CDK1 was observed. The expression of CDK1 in PCa samples was pronouncedly upregulated in terms of both the mRNA level and the protein level when compared with noncancer samples. Conclusion. miRNA-205 may play a vital role in PCa tumorigenesis and bone metastasis by targeting CDK1.

scholarly journals Decreased eGFR Is Associated With Ischemic Stroke in Patients With Dilated Cardiomyopathy

2019 ◽  
Vol 25 ◽  
pp. 107602961986690 ◽  
Author(s):  
Yuqing Deng ◽  
Zhiqing Chen ◽  
Lili Hu ◽  
Zhenyan Xu ◽  
Jinzhu Hu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Ischemic Stroke ◽  
Dilated Cardiomyopathy ◽  
Logistic Regression Analysis ◽  
Multivariate Logistic Regression Analysis ◽  
Analysis Model ◽  
Multivariate Logistic Regression ◽  
Increased Risk

Dilated cardiomyopathy (DCM) is increasingly indicated as a cause of cardioembolic syndrome, in particular, cardioembolic ischemia stroke. However, the potential risk factors for stroke among DCM patients remain under investigated. DCM patients hospitalized from June 2011 to June 2016 were included. The cases were defined as the group of DCM patients with stroke compared with those without stroke. Clinical characteristic data were collected and compared between the two groups including demographic data, complicated diseases, echocardiography index, and laboratory parameters and estimated glomerular filtration rate (eGFR). A multivariate logistic regression analysis model adjusted by sex and age was used to explore the related risk factors for stroke in DCM patients. A total of 779 hospitalized patients with DCM were included. Of these, 55 (7.1%) had experienced a stroke. Significantly lower eGFR levels (68.03 ± 26.22 vs 79.88 ± 24.25 mL/min/1.73 m2, P = .001) and larger left atrial diameters (45.32 ± 7.79 vs 43.25 ± 7.11 mm, P = .04) were found in the group of patients having DCM with stroke compared to those without stroke. When the eGFR was categorized as eGFR >60, 30<eGFR≤ 60 and eGFR ≤ 30, there were more patients with 30<eGFR≤ 60 (30.9% vs 17.7%) and eGFR≤ 30 (9.1% vs 3.3%) in the ischemic stroke group ( P = 0.003). A multivariate logistic regression analysis model adjusted by sex and age showed that 30 <eGFR≤60 (odds ratio [OR]: 2.07, 95% confidence interval [CI]: [1.05-4.07], P = .035) and eGFR≤30 (OR: 4.04, 95% CI: [1.41-11.62], P = .009) were statistically associated with ischemic stroke in patients with DCM. It is concluded that decreased eGFR is significantly associated with an increased risk of ischemic stroke in patients with DCM.

scholarly journals System Analysis of MIRNAs in Maize Internode Elongation

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 417
Author(s):  
Chuanxi Peng ◽  
Xing Wang ◽  
Tianyu Feng ◽  
Rui He ◽  
Mingcai Zhang ◽  
...  
Keyword(s):  
Target Genes ◽  
System Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Internode Elongation ◽  
Differentially Expressed Mirnas ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs), the post-transcriptional gene regulators, are known to play an important role in plant development. The identification of differentially expressed miRNAs could better help us understand the post-transcriptional regulation that occurs during maize internode elongation. Accordingly, we compared the expression of MIRNAs between fixed internode and elongation internode samples and classified six differentially expressed MIRNAs as internode elongation-responsive miRNAs including zma-MIR160c, zma-MIR164b, zma-MIR164c, zma-MIR168a, zma-MIR396f, and zma-MIR398b, which target mRNAs supported by transcriptome sequencing. Functional enrichment analysis for predictive target genes showed that these miRNAs were involved in the development of internode elongation by regulating the genes respond to hormone signaling. To further reveal how miRNA affects internode elongation by affecting target genes, the miRNA–mRNA–PPI (protein and protein interaction) network was constructed to summarize the interaction of miRNAs and these target genes. Our results indicate that miRNAs regulate internode elongation in maize by targeting genes related to cell expansion, cell wall synthesis, transcription, and regulatory factors.

scholarly journals Complications as important predictors of disability in ischemic stroke

2017 ◽  
Vol 36 (3) ◽  
pp. 197
Author(s):  
Rizaldy Taslim Pinzon ◽  
Rosa De Lima Renita Sanyasi
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Ischemic Stroke ◽  
Logistic Regression Analysis ◽  
Predictive Factors ◽  
Recurrent Stroke ◽  
Multiple Logistic Regression Analysis ◽  
Multiple Logistic Regression ◽  
Cross Sectional ◽  
Stroke Registry

Background<br />Stroke is the main cause of disability and death in many countries. The high incidence of disability in stroke survivors requires special attention to determine various predictive factors of disability. This study aimed to identify the various predictive factors of disability in ischemic stroke.<br /><br />Methods<br />This study was a cross sectional study on 4510 ischemic stroke patients. Each patient’s data had been recorded in the electronic stroke registry of Bethesda Hospital. Ischemic stroke diagnosis was confirmed by brain CT scan, which was interpreted by a neurologist and a radiologist. Disability was assessed using the modified Rankin scale. Predictors of disability were assessed. Multiple logistic regression analysis was used to analyse the data. <br /><br />Results<br />The subjects were predominantly males, &gt;60 years of age, and suffered stroke for the first time. The incidence of disability was 31.5% (1420/4510). Multiple logistic regression analysis showed that the presence of complications (OR: 6.43; 95% CI: 4.74-8.73; p&lt;0.001), decreased level of consciousness (OR: 4.82; 95% CI: 3.95-5.90; p &lt;0.001), onset ³3 hours (OR: 1.93; 95% CI: 1.52-2.45; p&lt;0.001), recurrent stroke (OR: 1.63; 95% CI: 1.39-1.90; p&lt;0.001), and age &gt;60 years (OR: 1.55; 95% CI: 1.35-1.79; p&lt;0.001) were independent predictive factors of disability.<br /><br />Conclusion<br />We demonstrated that a substantial proportion of patients with ischemic stroke become disabled. And the presence of complications was the most predictive factor of disability in ischemic stroke.

Sign in / Sign up

Export Citation Format

Share Document