scholarly journals Mitochondrial Disruption by Amyloid Beta 42 Identified by Proteomics and Pathway Mapping

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2380
Author(s):  
Patricia Sinclair ◽  
Ancha Baranova ◽  
Nadine Kabbani
Keyword(s):  
Amyloid Β ◽  
Enrichment Analysis ◽  
Peptide Mass Fingerprinting ◽  
Gene Set Enrichment Analysis ◽  
Ionization Mass ◽  
Related Gene ◽  
Gene Set Enrichment ◽  
Peptide Mass ◽  
Mitochondrial Disruption ◽  
New Biomarkers

Alzheimer’s disease (AD) is marked by chronic neurodegeneration associated with the occurrence of plaques containing amyloid β (Aβ) proteins in various parts of the human brain. An increase in several Aβ fragments is well documented in patients with AD and anti-amyloid targeting is an emerging area of therapy. Soluble Aβ can bind to various cell surface and intracellular molecules with the pathogenic Aβ42 fragment leading to neurotoxicity. Here we examined the effect of Aβ42 on network adaptations in the proteome of nerve growth factor (NGF) differentiated PC12 cells using liquid-chromatography electrospray ionization mass spectrometry (LC-ESI MS/MS) proteomics. Whole-cell peptide mass fingerprinting was coupled to bioinformatic gene set enrichment analysis (GSEA) in order to identify differentially represented proteins and related gene ontology (GO) pathways within Aβ42 treated cells. Our results underscore a role for Aβ42 in disrupting proteome responses for signaling, bioenergetics, and morphology in mitochondria. These findings highlight the specific components of the mitochondrial response during Aβ42 neurotoxicity and suggest several new biomarkers for detection and surveillance of amyloid disease.

scholarly journals Identification of Potential Prognostic Biomarker for Predicting Survival in Multiple Myeloma Using Bioinformatics Analysis and Experiments

2021 ◽  
Vol 12 ◽  
Author(s):  
Jian Zhou ◽  
Menghui Zhang ◽  
Yan Zhang ◽  
Xi Shi ◽  
Linlin Liu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gene Set Enrichment ◽  
Protein Protein Interaction ◽  
Kaplan Meier ◽  
New Biomarkers ◽  
Protein Protein Interaction Network

Multiple myeloma (MM) is a malignant disease of plasma cells, which remains incurable because of its unclear mechanism and drug resistance. Herein, we aimed to explore new biomarkers and therapeutic targets in MM. After screening differentially expressed genes (DEGs) in GSE6477 and GSE13591 dataset, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs using DAVID online database. The results indicated that the downregulated DEGs were mainly enriched in the immune-associated biological process. The protein–protein interaction network was constructed by STRING database, on which we performed module analysis and identified key genes. Gene set enrichment analysis (GSEA) and Kaplan–Meier analysis showed that RRM2 could be a novel biomarker in MM diagnosis. We further confirmed that novel RRM2 inhibitor osalmid inhibited MM cell proliferation and triggered cell cycle S phase arrest. Targeting RRM2 was expected to develop new therapeutic strategies for malignant MM.

scholarly journals Organoids Are Limited in Modeling the Colon Adenoma–Carcinoma Sequence

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 488
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Ankit Patel ◽  
Wanqing Tian ◽  
Li Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Immune Cells ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Related Gene ◽  
Gene Set Enrichment ◽  
Colon Adenoma ◽  
Tissue Samples ◽  
Gene Sets

The colon adenoma–carcinoma sequence is a multistep genomic-altering process that occurs during colorectal cancer (CRC) carcinogenesis. Organoids are now commonly used to model both non-cancerous and cancerous tissue. This study aims to investigate how well organoids mimic tissues in the adenoma–carcinoma sequence by comparing their transcriptomes. A total of 234 tissue samples (48 adenomas and 186 CRC) and 60 organoid samples (15 adenomas and 45 CRC) were analyzed. We found that cell-proliferation-related gene sets were consistently enriched in both CRC tissues and organoids compared to adenoma tissues and organoids by gene set enrichment analysis (GSEA). None of the known pathways in the colon adenoma–carcinoma sequence were consistently enriched in CRC organoids. There was no enrichment of the tumor microenvironment-related gene sets in CRC organoids. CRC tissues enriched immune-response-related gene sets, whereas CRC organoids did not. The proportions of infiltrating immune cells were different between tissues and organoids, whereas there was no difference between cancer and adenoma organoids. The amounts of cancer stem cells and progenitor cells were not different between CRC and adenoma organoids, whereas a difference was noted between CRC and adenoma tissues. In conclusion, we demonstrated that organoids model only part of the adenoma–carcinoma sequence and should be used with caution after considering their limitations.

Development and validation of an immune-related gene pairs signature in lower-grade glioma

2020 ◽  
Author(s):  
Xu Zhang ◽  
Shuai Ping ◽  
Rui Zhang ◽  
Can Li ◽  
Caibin Gao ◽  
...  
Keyword(s):  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Lower Grade ◽  
Related Gene ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Immune Related Gene ◽  
Lower Grade Glioma ◽  
Functional Pathways ◽  
Genome Atlas

Abstract Background Lower-grade gliomas (LGG) are the prevalent primary intracerebral malignancy tumor. Increasing evidence indicated an association between immune signature and LGG prognosis. Thus, we aim to develop an immune-related gene pairs (IRGPs) signature that can predict prognosis for LGG. Method: Gene expression levels and clinical information of LGG patients (LGGs) were collected from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. The two databases were divided into training cohort (n = 515) and an independent validation cohort (n = 604). IGRPs significantly associated with prognosis were selected by Cox regression. Gene set enrichment analysis and filtration were performed on IGRPs. Results Within 1991 immune genes, an 8 IRGPs signature including 15 unique genes was constructed, which had a significant association with survival. In the validation dataset, the IRGPs signature significantly stratified LGGs into low- and high-risk groups (P < 0.001), and it remained an independent prognostic factor in univariate and multivariate analyses (P < 0.001). Additionally, 26 functional pathways were filtrated through the intersection of Gene set enrichment analysis (GSEA) and gene ontology (GO) enrichment analysis. Conclusion The IGRPs signature demonstrated good prognostic value in lower-grade glioma, which may provide new insights into individual treatment for glioma patients. And the IGRPs might take effect through these filtrated 26 functional pathways.

scholarly journals Identification of Inflammatory Response-Related Gene Signature Associated With Immune Status and Prognosis of Lung Adenocarcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Weijie Zou ◽  
Li Chen ◽  
Wenwen Mao ◽  
Su Hu ◽  
Yuanqing Liu ◽  
...  
Keyword(s):  
High Risk ◽  
Inflammatory Response ◽  
Lung Adenocarcinoma ◽  
Immune Status ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
Related Gene ◽  
Gene Set Enrichment ◽  
Cox Analysis

Background: Lung adenocarcinoma (LUAD) is an exceedingly diverse disease, making prognostication difficult. Inflammatory responses in the tumor or the tumor microenvironment can alter prognosis in the process of the ongoing cross-talk between the host and the tumor. Nonetheless, Inflammatory response-related genes’ prognostic significance in LUAD, on the other hand, has yet to be determined.Materials and Methods: The clinical data as well as the mRNA expression patterns of LUAD patients were obtained from a public dataset for this investigation. In the TCGA group, a multigene prognostic signature was built utilizing LASSO Cox analysis. Validation was executed on LUAD patients from the GEO cohort. The overall survival (OS) of low- and high-risk cohorts was compared utilizing the Kaplan-Meier analysis. The assessment of independent predictors of OS was carried out utilizing multivariate and univariate Cox analyses. The immune-associated pathway activity and immune cell infiltration score were computed utilizing single-sample gene set enrichment analysis. GO keywords and KEGG pathways were explored utilizing gene set enrichment analysis.Results: LASSO Cox regression analysis was employed to create an inflammatory response-related gene signature model. The high-risk cohort patients exhibited a considerably shorter OS as opposed to those in the low-risk cohort. The prognostic gene signature’s predictive ability was demonstrated using receiver operating characteristic curve analysis. The risk score was found to be an independent predictor of OS using multivariate Cox analysis. The functional analysis illustrated that the immune status and cancer-related pathways for the two-risk cohorts were clearly different. The tumor stage and kind of immune infiltrate were found to be substantially linked with the risk score. Furthermore, the cancer cells’ susceptibility to anti-tumor medication was substantially associated with the prognostic genes expression levels.Conclusion: In LUAD, a new signature made up of 8 inflammatory response-related genes may be utilized to forecast prognosis and influence immunological state. Inhibition of these genes could also be used as a treatment option.

Construction of a Competitive Endogenous RNA Network Associated with Angiogenesis in Ischemic Stroke Using a Bioinformatics Approach

2021 ◽  
Author(s):  
Jia Wang ◽  
Xuxiang Zhang ◽  
Yibo Xie ◽  
Jiachen Li ◽  
Xiaokun Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Gene Set Enrichment ◽  
Differentially Expressed Mirnas ◽  
New Biomarkers ◽  
Competitive Endogenous Rna

Abstract Ischemic stroke (IS) is one of the leading causes of death and disability worldwide, and angiogenesis is an important target for its treatment. However, the mechanism of angiogenesis of endogenous RNA (ceRNA) in IS remains poorly understood. This study aims to explore the role of ceRNA in the angiogenesis of IS, to provide a possible target for the treatment of IS. First, GSE22255 (mRNA), GSE55937 (miRNA) and GSE102541 (lncRNA) were downloaded from the Gene Expression Omnibus (GEO) database. Then, a total of 21 mRNA modules were identified by WGCNA analysis, among which NR4A1, PTGS2, ERG3, and VEGFA in cyan module were identified as key genes for angiogenesis. Subsequently, 1454 differentially expressed lncRNAs (DELs) were screened and a lncRNA-mRNA co-expression network consisting of 40 lncRNAs and 4 mRNAs was constructed by correlation analysis. Then, 16 differentially expressed miRNAs (DEMs) were screened and the online database was used to predict the interaction information between miRNAs, lncRNAs and mRNAs. The angiogenesis-related ceRNA network was finally constructed based on ceRNA theory, in which 1 DEL was predicted as a ceRNA for 2 DEMs to regulate 4 hub genes, specifically, HCG18-has-let-7i-5p-NR4A1/PTGS2/ERG3, HCG18-miR-148a-3p-PTGS2/ERG3/VEGFA interaction axis. The results of gene set enrichment analysis (GSEA) suggest that HCG18 may regulate angiogenesis through NF-kB-TNFA signaling pathway, hypoxia and other pathways. In conclusion, the above genes may be new biomarkers and potential targets for the treatment of IS.

Identification of key mRNAs, miRNAs, and mRNA-miRNA network involved in papillary thyroid carcinoma

2020 ◽  
Vol 15 ◽  
Author(s):  
Wei Han ◽  
Dongchen Lu ◽  
Chonggao Wang ◽  
Mengdi Cui ◽  
Kai Lu
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Differential Expression Analysis ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Integrated Analysis ◽  
Papillary Thyroid ◽  
Gene Set Enrichment ◽  
Mirna Expression Data

Background: In the past decades, the incidence of thyroid cancer (TC) has been gradually increasing, owing to the widespread use of ultrasound scanning devices. However, the key mRNAs, miRNAs, and mRNA-miRNA network in papillary thyroid carcinoma (PTC) has not been fully understood. Material and Methods: In this study, multiple bioinformatics methods were employed, including differential expression analysis, gene set enrichment analysis, and miRNA-mRNA interaction network construction. Results: First, we investigated the key miRNAs that regulated significantly more differentially expressed genes based on GSEA method. Second, we searched for the key miRNAs based on the mRNA-miRNA interaction subnetwork involved in PTC. We identified hsa-mir-1275, hsa-mir-1291, hsa-mir-206 and hsa-mir-375 as the key miRNAs involved in PTC pathogenesis. Conclusion: The integrated analysis of the gene and miRNA expression data not only identified key mRNAs, miRNAs, and mRNA-miRNA network involved in papillary thyroid carcinoma, but also improved our understanding of the pathogenesis of PTC.

scholarly journals Placental Transcriptome Adaptations to Maternal Nutrient Restriction in Sheep

2021 ◽  
Vol 22 (14) ◽  
pp. 7654
Author(s):  
Chelsie B. Steinhauser ◽  
Colleen A. Lambo ◽  
Katharine Askelson ◽  
Gregory W. Burns ◽  
Susanta K. Behura ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Killer Cell ◽  
National Research Council ◽  
Enrichment Analysis ◽  
Nutrient Utilization ◽  
Gene Set Enrichment Analysis ◽  
Nutrient Restriction ◽  
Placental Development ◽  
Gene Set Enrichment ◽  
Pregnant Sheep

Placental development is modified in response to maternal nutrient restriction (NR), resulting in a spectrum of fetal growth rates. Pregnant sheep carrying singleton fetuses and fed either 100% (n = 8) or 50% (NR; n = 28) of their National Research Council (NRC) recommended intake from days 35–135 of pregnancy were used to elucidate placentome transcriptome alterations at both day 70 and day 135. NR fetuses were further designated into upper (NR NonSGA; n = 7) and lower quartiles (NR SGA; n = 7) based on day 135 fetal weight. At day 70 of pregnancy, there were 22 genes dysregulated between NR SGA and 100% NRC placentomes, 27 genes between NR NonSGA and 100% NRC placentomes, and 22 genes between NR SGA and NR NonSGA placentomes. These genes mediated molecular functions such as MHC class II protein binding, signaling receptor binding, and cytokine activity. Gene set enrichment analysis (GSEA) revealed significant overrepresentation of genes for natural-killer-cell-mediated cytotoxicity in NR SGA compared to 100% NRC placentomes, and alterations in nutrient utilization pathways between NR SGA and NR NonSGA placentomes at day 70. Results identify novel factors associated with impaired function in SGA placentomes and potential for placentomes from NR NonSGA pregnancies to adapt to nutritional hardship.

scholarly journals Higher Acid-Base Imbalance Associated with Respiratory Failure Could Decrease the Survival of Patients with Scrub Typhus during Intensive Care Unit Stay: A Gene Set Enrichment Analysis

2019 ◽  
Vol 8 (10) ◽  
pp. 1580 ◽  
Author(s):  
Kyoung Min Moon ◽  
Kyueng-Whan Min ◽  
Mi-Hye Kim ◽  
Dong-Hoon Kim ◽  
Byoung Kwan Son ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Respiratory Failure ◽  
Scrub Typhus ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Acid Base ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Gene Sets

Ninety percent of patients with scrub typhus (SC) with vasculitis-like syndrome recover after mild symptoms; however, 10% can suffer serious complications, such as acute respiratory failure (ARF) and admission to the intensive care unit (ICU). Predictors for the progression of SC have not yet been established, and conventional scoring systems for ICU patients are insufficient to predict severity. We aimed to identify simple and robust indicators to predict aggressive behaviors of SC. We evaluated 91 patients with SC and 81 non-SC patients who were admitted to the ICU, and 32 cases from the public functional genomics data repository for gene expression analysis. We analyzed the relationships between several predictors and clinicopathological characteristics in patients with SC. We performed gene set enrichment analysis (GSEA) to identify SC-specific gene sets. The acid-base imbalance (ABI), measured 24 h before serious complications, was higher in patients with SC than in non-SC patients. A high ABI was associated with an increased incidence of ARF, leading to mechanical ventilation and worse survival. GSEA revealed that SC correlated to gene sets reflecting inflammation/apoptotic response and airway inflammation. ABI can be used to indicate ARF in patients with SC and assist with early detection.

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