Nanopore Sequencing Reveals Global Transcriptome Signatures of Mitochondrial and Ribosomal Gene Expressions in Various Human Cancer Stem-like Cell Populations

Cancer stem cells (CSCs) are crucial mediators of tumor growth, metastasis, therapy resistance, and recurrence in a broad variety of human cancers. Although their biology is increasingly investigated within the distinct types of cancer, direct comparisons of CSCs from different tumor types allowing comprehensive mechanistic insights are rarely assessed. In the present study, we isolated CSCs from endometrioid carcinomas, glioblastoma multiforme as well as adenocarcinomas of lung and prostate and assessed their global transcriptomes using full-length cDNA nanopore sequencing. Despite the expression of common CSC markers, principal component analysis showed a distinct separation of the CSC populations into three clusters independent of the specific type of tumor. However, GO-term and KEGG pathway enrichment analysis revealed upregulated genes related to ribosomal biosynthesis, the mitochondrion, oxidative phosphorylation, and glycolytic pathways, as well as the proteasome, suggesting a great extent of metabolic flexibility in CSCs. Interestingly, the GO term “NF-kB binding” was likewise found to be elevated in all investigated CSC populations. In summary, we here provide evidence for high global transcriptional similarities between CSCs from various tumors, which particularly share upregulated gene expression associated with mitochondrial and ribosomal activity. Our findings may build the basis for identifying novel therapeutic strategies targeting CSCs.

Download Full-text

1H NMR-Based Analysis of Serum Metabolites in Monocrotaline-Induced Pulmonary Arterial Hypertensive Rats

Disease Markers ◽

10.1155/2016/5803031 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Taijie Lin ◽

Jinping Gu ◽

Caihua Huang ◽

Suli Zheng ◽

Xu Lin ◽

...

Keyword(s):

Intraperitoneal Injection ◽

Ventricular Hypertrophy ◽

Principal Component ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Metabolic Profiles ◽

Metabolic Dysfunction ◽

Sprague Dawley ◽

Mean Pulmonary Arterial Pressure ◽

Pulmonary Arterial

Aims. To study the changes of the metabolic profile during the pathogenesis in monocrotaline (MCT) induced pulmonary arterial hypertension (PAH).Methods. Forty male Sprague-Dawley (SD) rats were randomly divided into 5 groups (n=8, each). PAH rats were induced by a single dose intraperitoneal injection of 60 mg/kg MCT, while 8 rats given intraperitoneal injection of 1 ml normal saline and scarified in the same day (W0) served as control. Mean pulmonary arterial pressure (mPAP) was measured through catherization. The degree of right ventricular hypertrophy and pulmonary hyperplasia were determined at the end of first to fourth weeks; nuclear magnetic resonance (NMR) spectra of sera were then acquired for the analysis of metabolites. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to discriminate different metabolic profiles.Results. The prominent changes of metabolic profiles were seen during these four weeks. Twenty specific metabolites were identified, which were mainly involved in lipid metabolism, glycolysis, energy metabolism, ketogenesis, and methionine metabolism. Profiles of correlation between these metabolites in each stage changed markedly, especially in the fourth week. Highly activated methionine and betaine metabolism pathways were selected by the pathway enrichment analysis.Conclusions. Metabolic dysfunction is involved in the development and progression of PAH.

Download Full-text

Metabonomic-Transcriptome Integration Analysis on Osteoarthritis and Rheumatoid Arthritis

International Journal of Genomics ◽

10.1155/2020/5925126 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Ningyang Gao ◽

Li Ding ◽

Jian Pang ◽

Yuxin Zheng ◽

Yuelong Cao ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gap Junction ◽

Molecular Mechanisms ◽

Linear Models ◽

Principal Component ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Nf Kappa B ◽

Linear Module ◽

Hedgehog Acyltransferase

Purpose. This study is aimed at exploring the potential metabolite/gene biomarkers, as well as the differences between the molecular mechanisms, of osteoarthritis (OA) and rheumatoid arthritis (RA). Methods. Transcriptome dataset GSE100786 was downloaded to explore the differentially expressed genes (DEGs) between OA samples and RA samples. Meanwhile, metabolomic dataset MTBLS564 was downloaded and preprocessed to obtain metabolites. Then, the principal component analysis (PCA) and linear models were used to reveal DEG-metabolite relations. Finally, metabolic pathway enrichment analysis was performed to investigate the differences between the molecular mechanisms of OA and RA. Results. A total of 976 DEGs and 171 metabolites were explored between OA samples and RA samples. The PCA and linear module analysis investigated 186 DEG-metabolite interactions including Glycogenin 1- (GYG1-) asparagine_54, hedgehog acyltransferase- (HHAT-) glucose_70, and TNF receptor-associated factor 3- (TRAF3-) acetoacetate_35. Finally, the KEGG pathway analysis showed that these metabolites were mainly enriched in pathways like gap junction, phagosome, NF-kappa B, and IL-17 pathway. Conclusions. Genes such as HHAT, GYG1, and TRAF3, as well as metabolites including glucose, asparagine, and acetoacetate, might be implicated in the pathogenesis of OA and RA. Metabolites like ethanol and tyrosine might participate differentially in OA and RA progression via the gap junction pathway and phagosome pathway, respectively. TRAF3-acetoacetate interaction may be involved in regulating inflammation in OA and RA by the NF-kappa B and IL-17 pathway.

Download Full-text

Tissue-based metabolomics profiling reveals metabolic signatures and major metabolic pathways of gastric cancer

10.21203/rs.3.rs-326163/v1 ◽

2021 ◽

Author(s):

Yaqin Wang ◽

Wenchao Chen ◽

Kun Li ◽

Gang Wu ◽

Wei Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Predictive Ability ◽

Principal Component ◽

Enrichment Analysis ◽

Pentose Phosphate ◽

P Value ◽

Pathway Enrichment Analysis ◽

Dodecanoic Acid ◽

Orthogonal Projections ◽

Latent Structures

Abstract Purpose This study was aimed to screen differential metabolites between gastric cancer (GC) and paracancerous (PC) tissues and find new biomarkers of GC. Methods GC (n = 28) and matched PC (n = 28) tissues were collected and LC-MS/MS analyses were performed to detect metabolites of GC and PC tissues in positive and negative models. Principal component analysis (PCA) and orthogonal projections to latent structures-discriminate analysis (OPLS-DA) were conducted to describe distribution of origin data and general separation and estimate the robustness and the predictive ability of our mode. Differential metabolites were screened based on criterion of variables with p value < 0.05 and VIP (variable importance in the projection) > 1.0. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic power of differential metabolites. Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to search for metabolite pathways and MetaboAnalyst was used for pathway enrichment analysis. Results Several metabolites were significantly changed in GC group compared with PC group. Thirteen metabolites with high VIP were chose and among which 1-methylnicotinamide, dodecanoic acid and sphinganine possessed high AUC values (AUC > 0.8) indicating an excellent discriminatory ability on GC. Pathways such as pentose phosphate pathway and histidine metabolism were focused based on differential metabolites demonstrating their effects on progress of GC. Conclusions In conclusion, we investigated the tissue-based metabolomics profile of GC and several differential metabolites and signaling pathways were focused. Further study is needed to verify those results.

Download Full-text

Plasma Metabolic Profiling of Pediatric Sepsis in a Chinese Cohort

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.643979 ◽

2021 ◽

Vol 9 ◽

Author(s):

Guo-Bang Li ◽

Hong-Rong Hu ◽

Wen-Feng Pan ◽

Bo Li ◽

Zhi-Ying Ou ◽

...

Keyword(s):

Fatty Acids ◽

Pathogenic Bacteria ◽

Bacterial Species ◽

Disease Onset ◽

Principal Component ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Control Subjects ◽

Sepsis Survivors ◽

Pediatric Sepsis

Sepsis represents one of the most pressing problems in pediatrics, characterized by pathogenic bacteria invading the blood, growing and multiplying in the blood circulation, and ultimately causing severe infections. Most children with sepsis have a rapid disease onset and frequently exhibit sudden high fever or first chills. Here we performed comprehensive metabolomic profiling of plasma samples collected from pediatric sepsis patients to identify specific metabolic alterations associated with these patients (n = 84, designated as case subjects) as compared to healthy cohorts (n = 59, designated as control subjects). Diagnostic models were constructed using MetaboAnalyst, R packages, and multiple statistical methods, such as orthogonal partial least squares-discriminant analysis, principal component analysis, volcano plotting, and one-way ANOVA. Our study revealed a panel of metabolites responsible for the discrimination between case and control subjects with a high predictive value of prognosis. Moreover, significantly altered metabolites in sepsis survivors versus deceased patients (non-survivors) were identified as those involved in amino acids, fatty acids, and carbohydrates metabolism. Nine metabolites including organic acids and fatty acids were also identified with significantly higher abundance in sepsis patients with related microbes, implicating greater potentials to distinguish bacterial species using metabolomic analysis than blood culture. Pathway enrichment analysis further revealed that fatty acid metabolism might play an important role in the pathogenesis of sepsis.

Download Full-text

Multi-omics analysis of m6A modification-related patterns based on m6A regulators and tumor microenvironment infiltration in lung adenocarcinoma

Scientific Reports ◽

10.1038/s41598-021-00272-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xincheng Wu ◽

Zhengping Bai

Keyword(s):

Tumor Microenvironment ◽

Lung Adenocarcinoma ◽

Cytotoxic T Lymphocyte ◽

Principal Component ◽

Enrichment Analysis ◽

Comprehensive Analysis ◽

Survival Advantage ◽

Pathway Enrichment Analysis ◽

Mutation Burden

AbstractEpigenetic modifications, especially N6-methyladenosine (m6A) modification, play a key role in tumor microenvironment (TME) infiltration. However, the regulatory role of m6A modification in the TME of lung adenocarcinoma (LUAD) remains unclear. A total of 2506 patients with LUAD were included in the analysis and divided into different groups according to distinct m6A modification-related patterns based on 23 m6A regulators. A comprehensive analysis was performed to explore TME infiltration in different m6A modification-related patterns. Principal component analysis was performed to obtain the m6Ascore and to quantify m6A modification-related patterns in different individuals. Three distinct m6A modification-related patterns were identified by 23 m6A regulators. The pathway enrichment analysis showed that m6Acluster-A was associated with immune activation; m6Acluster-B was associated with carcinogenic activation; m6Acluster-C was prominently related to substance metabolism. M6Acluster-A was remarkably rich in TME-infiltrating immune cells and patients with this pattern showed a survival advantage. The m6Ascore could predict TME infiltration, tumor mutation burden (TMB), the effect of tumor immunotherapy, and the prognosis of patients in LUAD. High m6Ascore was characterized by increased TME infiltration, reduced TMB, and survival advantage. Patients with a high m6Ascore exhibited significantly improved clinical response to anti-cytotoxic T lymphocyte antigen-4 (anti-CTLA4) immunotherapy. This study explored the regulatory mechanisms of TME infiltration in LUAD. The comprehensive analysis of m6A modification-related patterns may contribute to the development of individualized immunotherapy and the improvement of the overall effectiveness of immunotherapy for LUAD patients.

Download Full-text

SARS-CoV-2 Infections - Gene Expression Omnibus (GEO) Data Mining, Pathway Enrichment Analysis, and Prediction of Repurposable Drugs/Compounds

10.20944/preprints202009.0459.v1 ◽

2020 ◽

Author(s):

Srilakshmi Chaparala ◽

Carrie L Iwema ◽

Ansuman Chattopadhyay

Keyword(s):

Gene Expression ◽

Oxidative Phosphorylation ◽

Mitochondrial Dysfunction ◽

Enrichment Analysis ◽

Gene Expression Omnibus ◽

Host Cells ◽

In Vivo Studies ◽

Pathway Enrichment Analysis ◽

Gene Expressions ◽

Pathway Enrichment

The COVID-19 global pandemic has created dire consequences with an alarming rate of morbidity and mortality. There are not yet vaccine or efficacious treatment options to combat the causative SARS-CoV-2 infection. This paper describes the identification of potentially repurposable drugs for COVID-19 treatment by conducting pathway enrichment analysis on publicly available Gene Expression Omnibus datasets. We first determined SARS-CoV-2 infection-induced alterations of host gene expressions and pathways. We then identified drugs or compounds that target and counter virus-triggered cellular perturbations, suggesting their potential repurposing for COVID-19 treatment. The key findings are that SARS-CoV-2 infection in host cells induces mitochondrial dysfunction, inhibits oxidative phosphorylation, and activates several immune response and pro-inflammatory pathways. Triptolide, the major bioactive component of a traditional Chinese medicine herb, may rescue mitochondrial dysfunction by activating oxidative phosphorylation. Further in vitro and in vivo studies are necessary to verify these results prior to clinical application.

Download Full-text

SHMT2 is Associated with Tumor Purity, CD8+ T Immune Cells Infiltration, and a Novel Therapeutic Target in Four Different Human Cancers

Current Molecular Medicine ◽

10.2174/1566524022666220112142409 ◽

2022 ◽

Vol 22 ◽

Author(s):

Muhammad Usman ◽

Yasir Hameed ◽

Mukhtiar Ahmad ◽

Muhammad Junaid Iqbal ◽

Aghna Maryam ◽

...

Keyword(s):

Immune Cells ◽

Promoter Methylation ◽

In Silico ◽

Human Cancer ◽

Enrichment Analysis ◽

Genetic Alterations ◽

Pathway Enrichment Analysis ◽

Human Cancers ◽

Tumor Purity

Aims: This study was launched to identify the SHMT2 associated Human Cancer subtypes. Background: Cancer is the 2nd leading cause of death worldwide. Previous reports revealed the limited involvement of SHMT2 in human cancer. In the current study, we comprehensively analyzed the role of SHMT2 in 24 major subtypes of human cancers using in silico approach and identified a few subtypes that are mainly associated with SHMT2. Objective:: We aim to comprehensively analyze the role of SHMT2 in 24 major subtypes of human cancers using in silico approach and identified a few subtypes that are mainly associated with SHMT2. Earlier, limited knowledge exists in the medical literature regarding the involvement of Serine Hydroxymethyltransferase 2 (SHMT2) in human cancer. Methods: In the current study, we comprehensively analyzed the role of SHMT2 in 24 major subtypes of human cancers using in silico approach and identified a few subtypes that are mainly associated with SHMT2. Pan-cancer transcriptional expression profiling of SHMT2 was done using UALCAN while further validation was performed using GENT2. For translational profiling of SHMT2, we utilized Human Protein Atlas (HPA) platform. Promoter methylation, genetic alteration, and copy number variations (CNVs) profiles were analyzed through MEXPRESS and cBioPortal. Survival analysis was carried out through Kaplan–Meier (KM) plotter platform. Pathway enrichment analysis of SHMT2 was performed using DAVID, while the gene-drug network was drawn through CTD and Cytoscape. Furthermore, in the tumor microenvironment, a correlation between tumor purity, CD8+ T immune cells infiltration, and SHMT2 expression was accessed using TIMER. Results: SHMT2 was found overexpressed in 24 different subtypes of human cancers and its overexpression was significantly associated with the reduced Overall survival (OS) and Relapse-free survival durations of Breast cancer (BRCA), Kidney renal papillary cell carcinoma (KIRP), Liver hepatocellular carcinoma (LIHC), and Lung adenocarcinoma (LUAD) patients. This implies that SHMT2 plays a significant role in the development and progression of these cancers. We further noticed that SHMT2 was also up-regulated in BRCA, KIRP, LIHC, and LUAD patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of SHMT2 enriched genes in five diverse pathways. Furthermore, we also explored some interesting correlations between SHMT2 expression and promoter methylation, genetic alterations, CNVs, tumor purity, and CD8+ T immune cell infiltrates. Conclusion: Our results suggested that overexpressed SHMT2 is correlated with the reduced OS and RFS of the BRCA, KIRP, LIHC, and LUAD patients and can be a potential diagnostic and prognostic biomarker for these cancers.

Download Full-text

Subtypes of Histopathologically Classical Aldosterone-Producing Adenomas Yield Various Transcriptomic Signaling and Outcomes

Hypertension ◽

10.1161/hypertensionaha.121.18006 ◽

2021 ◽

Author(s):

Vin-Cent Wu ◽

Kang-Yung Peng ◽

Yu-Ping Kuo ◽

Hsuan Liu ◽

Bertrand Chin-Ming Tan ◽

...

Keyword(s):

Primary Aldosteronism ◽

Clinical Success ◽

Enrichment Analysis ◽

Mechanistic Explanation ◽

Pathway Enrichment Analysis ◽

Gene Expressions ◽

Analysis Group ◽

Group A ◽

Outcome Differences ◽

Group B

There have been no reports of outcome differences between distinctive subgroups in patients with unilateral primary aldosteronism with histopathologically classical adenomas. The characteristics and incidence of complete clinical success in the patients with unilateral primary aldosteronism could be associated with the concomitant existence of multiple aldosterone-producing micronodules/nodules. Altogether, 74 classical adenomas (mean, 52.9 years and 40 men [54.1%]) were identified among 98 operated patients with unilateral primary aldosteronism. Among them accompanying multiple aldosterone-producing micronodules/nodules (group A) were identified in 38 (51.3%) of the adrenal glands; these patients showed lower likelihood (42.1%) to achieve complete clinical success than that (80.6%) of those with aldosterone-producing adenoma/nodules alone (group B, P =0.001). Additionally, group A adenomas were associated with less complete clinical success (odds ratio, 5.53, P =0.005) in the multivariable regression analysis. Group A patients also had higher baseline aldosterone production (absolute aldosterone ratio) from the contralateral adrenal gland ( P =0.039). Based on the patterns of genes with highly differential expressions as uncovered by RNA-seq analysis, Group A adenomas showed distinct transcriptomic profiles in comparison to the gene expressions from Group B adenomas. Pathway enrichment analysis revealed that HTR2B-mediated calcium pathway, in terms of HTR2B , and PLCE1 was prominently downregulated in Group A adenomas. There was 51.3% of the patients with unilateral primary aldosteronism with classical group A adenomas. These patients were more likely to have hypertension-persistence after adrenalectomy. The functional signatures of Group A adenomas showed attenuated HTR2B-mediated PLC/IP3/Ca2 + pathway; this may provide some mechanistic explanation to various clinical outcomes.

Download Full-text

CSF microRNAs discriminate MS activity and share similarity to other neuroinflammatory disorders

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000673 ◽

2020 ◽

Vol 7 (2) ◽

pp. e673

Author(s):

Océane Perdaens ◽

Hong Anh Dang ◽

Ludovic D'Auria ◽

Vincent van Pesch

Keyword(s):

Disease Activity ◽

Mirna Expression ◽

Inflammatory Diseases ◽

Principal Component ◽

In Silico Analysis ◽

Enrichment Analysis ◽

Mirna Expression Profile ◽

Pathway Enrichment Analysis ◽

Peripheral Blood Mononuclear ◽

Cross Sectional

ObjectiveTo perform a comprehensive multicompartment analysis of microRNA (miRNA) expression in multiple sclerosis (MS) linked to disease activity and compared with other neuroinflammatory diseases through a retrospective cross-sectional study.MethodsOne hundred twenty-seven miRNAs were measured by PCR arrays on pooled CSF, serum, and peripheral blood mononuclear cell (PBMC) samples of 10 patients with relapsing MS and 10 controls. Sixty-four miRNAs were then measured by quantitative PCR on individual CSF samples of patients with relapsing or remitting MS and controls (n = 68). Fifty-seven miRNAs were analyzed in the CSF from a second cohort (n = 75), including patients with MS, neuroinfectious, or neuroinflammatory diseases and controls. MiRNAs significantly dysregulated in the CSF were analyzed on individual serum/PBMC samples (n = 59/48) of patients with relapsing or remitting MS and controls. Post hoc analysis consisted of principal component analysis (PCA), gene set, and pathway enrichment analysis.ResultsTwenty-one miRNAs were differentially expressed, mainly upregulated in the CSF during MS relapses. Relapsing MS and neuroinfectious/inflammatory diseases exhibited a partially overlapping CSF miRNA expression profile. Besides confirming the association of miR-146a-5p/150-5p/155-5p with MS, 7 miRNAs uncharacterized for MS emerged (miR-15a-3p/124-5p/149-3p/29c-3p/33a-3p/34c-5p/297). PCA showed that distinct miRNA sets segregated MS from controls and relapse from remission. In silico analysis predicted the involvement of these miRNAs in cell cycle, immunoregulation, and neurogenesis, but also revealed that the signaling pathway pattern of remitting MS is more akin to controls rather than patients with relapsing MS.ConclusionsThis study highlights the CSF-predominant dysregulation of miRNAs in MS by identifying a signature of disease activity and intrathecal inflammation among neuroinflammatory disorders.

Download Full-text

Up-regulation of GINS1 highlighted a good diagnostic and prognostic potential of survival in three different subtypes of human cancer

Brazilian Journal of Biology ◽

10.1590/1519-6984.250575 ◽

2024 ◽

Vol 84 ◽

Author(s):

M. Ahmad ◽

Y. Hameed ◽

M. Khan ◽

M Usman ◽

A. Rehman ◽

...

Keyword(s):

Immune Cells ◽

Promoter Methylation ◽

Prognostic Biomarker ◽

Human Cancer ◽

Interaction Network ◽

Enrichment Analysis ◽

Copy Number Variations ◽

Pathway Enrichment Analysis ◽

Poor Overall Survival ◽

Cancer Subtypes

Abstract Cancer is a fatal malignancy and its increasing worldwide prevalence demands the discovery of more sensitive and reliable molecular biomarkers. To investigate the GINS1 expression level and its prognostic value in distinct human cancers using a series of multi-layered in silico approach may help to establish it as a potential shared diagnostic and prognostic biomarker of different cancer subtypes. The GINS1 mRNA, protein expression, and promoter methylation were analyzed using UALCAN and Human Protein Atlas (HPA), while mRNA expression was further validated via GENT2. The potential prognostic values of GINS1 were evaluated through KM plotter. Then, cBioPortal was utilized to examine the GINS1-related genetic mutations and copy number variations (CNVs), while pathway enrichment analysis was performed using DAVID. Moreover, a correlational analysis between GINS1 expression and CD8+ T immune cells and a the construction of gene-drug interaction network was performed using TIMER, CDT, and Cytoscape. The GINS1 was found down-regulated in a single subtypes of human cancer while commonly up-regulated in 23 different other subtypes. The up-regulation of GINS1 was significantly correlated with the poor overall survival (OS) of Liver Hepatocellular Carcinoma (LIHC), Lung Adenocarcinoma (LUAD), and Kidney renal clear cell carcinoma (KIRC). The GINS1 was also found up-regulated in LIHC, LUAD, and KIRC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of GINS1 in two diverse pathways, while few interesting correlations were also documented between GINS1 expression and its promoter methylation level, CD8+ T immune cells level, and CNVs. Moreover, we also predicted few drugs that could be used in the treatment of LIHC, LUAD, and KIRC by regulating the GINS1 expression. The expression profiling of GINS1 in the current study has suggested it a novel shared diagnostic and prognostic biomarker of LIHC, LUAD, and KIRC.

Download Full-text