scholarly journals Comprehensive Pan-Cancer Analysis and the Regulatory Mechanism of ASF1B, a Gene Associated With Thyroid Cancer Prognosis in the Tumor Micro-Environment

2021 ◽  
Vol 11 ◽  
Author(s):  
Jing Ma ◽  
Wei Han ◽  
Kai Lu
Keyword(s):  
Gene Expression ◽  
Survival Analysis ◽  
Thyroid Cancer ◽  
Prognostic Marker ◽  
Enrichment Analysis ◽  
Differential Analysis ◽  
Expression Levels ◽  
Multiple Cancers ◽  
Mtorc1 Signaling ◽  
Pan Cancer

BackgroundThe incidence of thyroid cancer, whose local recurrence and metastasis lead to death, has always been high and the pathogenesis of papillary thyroid carcinoma (PTC) has not been clearly elucidated. Therefore, the research for more accurate prognosis-related predictive biomarkers is imminent, and a key gene can often be a prognostic marker for multiple tumors.MethodsGene expression profiles of various cancers in the TCGA and GTEx databases were downloaded, and genes significantly associated with the prognosis of THCA were identified by combining differential analysis with survival analysis. Then, a series of bioinformatics tools and methods were used to analyze the expression of the gene in each cancer and the correlation of each expression with prognosis, tumor immune microenvironment, immune neoantigens, immune checkpoints, DNA repair genes, and methyltransferases respectively. The possible biological mechanisms were also investigated by GSEA enrichment analysis.Results656 differentially expressed genes were identified from two datasets and 960 DEGs that were associated with disease-free survival in THCA patients were screened via survival analysis. The former and the latter were crossed to obtain 7 key genes, and the gene with the highest risk factor, ASF1B, was selected for this study. Differential analysis of multiple databases showed that ASF1B was commonly and highly expressed in pan-cancer. Survival analysis showed that high ASF1B expression was significantly associated with poor patient prognosis in multiple cancers. In addition, ASF1B expression levels were found to be associated with tumor immune infiltration in THCA, KIRC, LGG, and LIHC, and with tumor microenvironment in BRCA, LUSC, STAD, UCEC, and KIRC. Further analysis of the relationship between ASF1B expression and immune checker gene expression suggested that ASF1B may regulate tumor immune patterns in most tumors by regulating the expression levels of specific immune checker genes. Finally, GSEA enrichment analysis showed that ASF1B high expression was mainly enriched in cell cycle, MTORC1 signaling system, E2F targets, and G2M checkpoints pathways.ConclusionsASF1B may be an independent prognostic marker for predicting the prognosis of THCA patients. The pan-cancer analysis suggested that ASF1B may play an important role in the tumor micro-environment and tumor immunity and it has the potential of serving as a predictive biomarker for multiple cancers.

MiRNA-4665-3p Regulates Expression of PLD5 in Thyroid Cancer Patients and Predicts Death

2019 ◽  
Vol 9 (7) ◽  
pp. 871-880
Author(s):  
Yifan Han ◽  
Lei Zhou
Keyword(s):  
Survival Analysis ◽  
Thyroid Cancer ◽  
Cancer Patients ◽  
Microarray Data ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Core Gene ◽  
Differential Analysis ◽  
The Core ◽  
Differential Genes

Thyroid cancer has become an increasingly common malignant tumor around the world, and its incidence is increasing year by year. In this study, mRNA microarray data of thyroid cancer patients from four periods were collected from the TCGA database. We performed a series of bioinformatics analyses on these mRNA expression profiles, including differential analysis, co-expression analysis, enrichment analysis, regulator prediction, and survival analysis. There were 13126, 10914, 13585, and 13241 differential genes in the four periods; 4822 differential genes were obtained by union and deduplication (p < 0.01). Weighted gene co-expression network analysis indicated a total of 21 functional disorder modules. In each module, PLD5, CHD4, ADGRA3, ITGA3, etc. were the key genes. Enrichment analysis showed that the dysfunctional module genes were mainly related to pre-replicative complex assembly, Cytokine–cytokine receptor interaction, and MAPK signaling pathway. We downloaded thyroid cancer-associated miRNA microarray data from the GEO database for differential analysis. Then, we crossed the predicted ncRNA with the differential miRNA to obtain thyroid cancer-associated regulatory factors. Finally, we found that miRNA-4665-3p regulates the core gene PLD5, and six regulators such as miRNA-3140-3p and miRNA-324-3p regulate the core gene CHD4. Survival analysis showed that both up-regulation of PLD5 expression and down-regulation of CHD4 expression accelerated patient death. According to the above analysis, we believe miRNA-4665-3p regulates the expression of PLD5 and affects the development of thyroid cancer. Its up-regulation promotes the death of patients.

scholarly journals Pan-Cancer Analysis of Atrial-Fibrillation-Related Innate Immunity Gene ANXA4

2021 ◽  
Vol 8 ◽  
Author(s):  
Tao Yan ◽  
Shijie Zhu ◽  
Yu Shi ◽  
Changming Xie ◽  
Miao Zhu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Survival Analysis ◽  
Sinus Rhythm ◽  
Enrichment Analysis ◽  
Related Gene ◽  
Expression Levels ◽  
Immune Infiltration ◽  
Immune Related Gene ◽  
Cancer Types ◽  
Pan Cancer

Background: Atrial fibrillation (AF) is the most common tachyarrhythmia around the world. Cancer is one of the main causes of death worldwide. A recent study demonstrated that cancer was associated with an increased incidence of AF. In the present study, we aimed to explore possible mechanisms and potential common therapeutic targets between AF and cancer.Methods: Differentially expressed proteins between AF and sinus rhythm were identified utilizing proteomics analysis. Weighted gene correlation network analysis was applied to cluster proteins into different modules and investigate associations between modules and AF. Hub immune-related genes were selected via InnateDB database and verified using qRT-PCR. RNA sequencing and clinical data of 33 different cancer types were achieved from The Cancer Genome Atlas (TCGA). The correlations between ANXA4 expression and the prognosis were calculated utilizing Cox regression analysis and Kaplan-Meier survival analysis. Spearman's rank correlation test was used to assess associations between ANXA4 and immune infiltration and DNA methylation. Enrichment analysis was performed through gene ontology and gene set enrichment analysis (GSEA).Results:ANXA4 was identified as hub immune-related gene between AF and sinus rhythm. Expression levels of ANXA4 increased in diverse cancer types. Survival analysis suggested prognostic significance of ANXA4 expression levels in various cancer types. Immune correlation analysis indicated that ANXA4 expression levels were associated with tumor immune infiltration in most cancer types. ANXA4 might influence the efficacy of immunotherapy via tumor burden and microsatellite instability. GSEA results indicated that high ANXA4 expression groups were mainly enriched in peroxisome, bile acid biosynthesis, and p53 pathway.Conclusion:ANXA4 was identified as a hub immune-related gene in AF, which has never been reported. Pan-cancer analysis indicated its potential as a novel clinical prognostic marker and therapeutic target in diverse cancer types. ANXA4 might play crucial roles in AF and cancer, and targeted therapy for ANXA4 might reduce the incidence of AF in cancer patients.

scholarly journals GPX7 is Identified as a Novel Prognostic Indicator for Brain Lower Grade Glioma (LGG): Evidence from a Pan-Cancer Analysis

2021 ◽  
Author(s):  
Qianqian Zhao ◽  
Yin Yang ◽  
Luyu Zhang ◽  
Yingying Wang ◽  
Tianpei Wang ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Poor Prognosis ◽  
Enrichment Analysis ◽  
Prognostic Indicator ◽  
Lower Grade ◽  
Free Survival ◽  
Multiple Tumors ◽  
Expression Levels ◽  
Lower Grade Glioma ◽  
Pan Cancer

Abstract Background: Glutathione peroxidase-7 (GPX7), a newly discovered non-selenium-containing protein with glutathione peroxidase activity, is located near the endoplasmic reticulum. Various studies have reported the involvement of GPX7 in cancer disease progression. However, the expression patterns of GPX7 and its prognostic potential have not been evaluated from a pan-cancer perspective. Moreover, the relationship between GPX7 and prognosis in Brain Lower Grade Glioma (LGG) patients remains unclear.Methods: Expression levels of GPX7 were evaluated using the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA2) were used to evaluate the effect of GPX7 on clinical prognosis in TCGA tumors. Correlations between GPX7 and cancer immune infiltrates were investigated using the Tumor Immune Estimation Resource (TIMER) site and Estimating the Proportions of Immune and Cancer cells (EPIC) algorithm. In addition, the GEPIA2 and STRING websites were used for enrichment analysis of GPX7-related genes. Finally, we constructed a prognostic Nomogram for LGG to verify the overall survival (OS) outcomes of patients.Results: GPX7 was found to be overexpressed in multiple tumors. Elevated expression levels of GPX7 were associated with poor prognosis regarding OS, disease-free survival (DFS) and progression-free survival (PFS) of LGG patients (OS Hazard ratio (HR) = 1.044, p < 0.0001; DFS HR = 1.035, p < 0.0001; PFS HR = 1.045, p < 0.0001). Concordance index (C-index) of the nomogram for LGG was 0.845 (95% CI, 0.825 to 0.865; p < 0.001). The nomogram exhibited a better predictability. In addition, GPX7 expression and the abundance of Cancer-associated fibroblasts (CAFs) were positively correlated in most cancer types. Enrichment analysis revealed that GPX7 may be involved in the glutathione derivative biosynthetic and glutathione metabolic biological processes.Conclusion: GPX7 was found to be upregulated in multiple tumors, which was correlated with poor prognosis in LGG. Therefore, GPX7 is a potential prognostic indicator for LGG. There is a strong correlation between GPX7 expression levels and glutathione metabolic pathways. GPX7 holds promise for the use of glutathione metabolism for guided therapy in cancer patients.

scholarly journals Identification and Validation of Hub Genes Associated With Hepatocellular Carcinoma Via Integrated Bioinformatics Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Sumei Wang ◽  
Zuoli Song ◽  
Bing Tan ◽  
Jinjuan Zhang ◽  
Jiandong Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Survival Analysis ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Functional Enrichment ◽  
High Morbidity ◽  
Hub Genes ◽  
Study Gene Expression

Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver, with high morbidity and mortality, yet its molecular mechanisms of tumorigenesis are still unclear. In this study, gene expression profile of GSE62232 was downloaded from the Gene Expression Omnibus (GEO). The RNA-seq expression data and relative clinical information were retrieved from the Cancer Genome Atlas (TCGA) database. The datasets were analyzed by differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) to obtain the overlapping genes. Then, we performed a functional enrichment analysis to understand the potential biological functions of these co-expression genes. Finally, we constructed the protein-protein interaction (PPI) analysis combined with survival analysis. MARCO, CLEC4M, FCGR2B, LYVE1, TIMD4, STAB2, CFP, CLEC4G, CLEC1B, FCN2, FCN3 and FOXO1 were identified as the candidate hub genes using the CytoHubba plugin of Cytoscape. Based on survival analysis, the lower expression of FCN3 and FOXO1 were associated with worse overall survival (OS) in HCC patients. Furthermore, the expression levels of FCN3 and FOXO1 were validated by the Human Protein Atlas (HPA) database and the qRT-PCR. In summary, our findings contribute new ideas for the precise early diagnosis, clinical treatment and prognosis of HCC in the future.

scholarly journals Identification of Hub Genes Associated With Progression and Prognosis of Bladder Cancer by Integrated Bioinformatics Analysis.

2021 ◽  
Author(s):  
Daoquan Liu ◽  
Jianhong Ma ◽  
Sheng Wei ◽  
Jianmin Liu ◽  
Mingzhou Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Muscle Contraction ◽  
Focal Adhesion ◽  
Enrichment Analysis ◽  
Hub Genes ◽  
Expression Levels ◽  
Qrt Pcr ◽  
Go Enrichment ◽  
Go Enrichment Analysis

Abstract Background: Bladder cancer (BLCA) is the most popular malignant carcinomas in genitourinary system which has a high incidence and is prone to relapse. However, the molecular mechanism of BLCA remains to be unclear. Moreover, there is still a shortage of effective biomarkers that can predict progression and prognosis of BLCA. The objective of current study is to screen significant genes as biomarkers to forecast the progression and prognosis of BLCA patients.Methods: Gene expression profile downloaded from TCGA database and GEO database was used. Differential gene expression analysis and WGCNA were conducted to identify differential co-expression genes. In addition, GO enrichment analysis and KEGG pathway analysis were used to explore the functions of these genes. Moreover, PPI network, OS and DFS were used to identify survival-related hub genes. Finally, the expression levels of these genes were validated by qRT-PCR and HPA database.Results: About 124 differential co-expression genes were identified. And these genes were mainly enriched in muscle system process and muscle contraction (BP), contractile fiber, myofibril, sarcomere, focal adhesion and cell-substrate junction (CC) and actin binding (MF) in GO enrichment analysis, while enriched in vascular smooth muscle contraction, focal adhesion, cardiac muscle contraction, hypertrophic cardiomyopathy, dilated cardiomyopathy and regulation of actin cytoskeleton in KEGG analysis. Furthermore, five survival-related hub genes (MYH11, ACTA2, CALD1, TPM1, MYLK) were identified via overall OS and DFS. In addition, the expression levels of the five survival-related genes were upregulated with the procession of BLCA, such as grade, stage and TNM stage. Finally, all survival-related hub genes were found to be down-regulated in BLCA via qRT-PCR and HPA database.Conclusions: Our current study verified five new key genes in BLCA, which could help us better understand the pathogenesis of BLCA. And these five hub genes may be involved in the development and progression of BLCA and served as potential biomarkers.

scholarly journals Integrated bioinformatics analysis and screening hub genes in papillary thyroid cancer

2020 ◽  
Author(s):  
Rong Fan ◽  
Lijin Dong ◽  
Ping Li ◽  
Xiaoming Wang ◽  
Xuewei Chen
Keyword(s):  
Gene Ontology ◽  
Survival Analysis ◽  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Enrichment Analysis ◽  
Analysis Tool ◽  
Papillary Thyroid ◽  
Hub Genes ◽  
New Biomarkers ◽  
Online Software

Abstract Background With the increasing incidence, papillary thyroid cancer (PTC) is receiving more and more attention, but the pathogenesis of which is still not completely elucidated. The purpose of this study was to explore key biomarkers and new therapeutic targets in PTC. Methods GEO2R and Venn online software were used for differential gene screening analysis. Hub genes were screened via STRING and Cytoscape, following Gene Ontology and KEGG enrichment analysis. Finally, survival analysis and expression validation were performed via UALCAN online software and immunohistochemistry. Results We screened 334 consistently differentially expressed genes (DEGs), composed of 136 upregulated genes and 198 downregulated genes. Gene ontology enrichment analysis suggested that DEGs mainly enriched in the cancer-related pathways and functions. PPI network visualization was performed to select 17 upregulated and 13 downregulated DEGs. Finally, the expression verification and overall survival analysis conducted in the Gene Expression Profiling Interactive Analysis Tool (GEPIA) and UALCAN showed that LPAR5, TFPI and ENTPD1 were related to the development of PTC and the prognosis of PTC patients, and the expression of LPAR5 was verified by tissue chip. Conclusions In summary, the hub genes and pathways identified in the present study not only provided new biomarkers for PTC, but also will be useful for elucidating the pathogenesis of PTC.

scholarly journals Transcriptome analysis of the regulation of natamycin biosynthesis in Streptomyces natalensis HW-2 by fungal elicitor

2019 ◽  
Author(s):  
Dahong Wang ◽  
Wenhao Shen ◽  
Jiangfeng Yuan ◽  
Lanlan Wei ◽  
Ying Zhang
Keyword(s):  
Gene Expression ◽  
Transcriptome Analysis ◽  
Tricarboxylic Acid Cycle ◽  
Enrichment Analysis ◽  
Pentose Phosphate ◽  
Fungal Elicitor ◽  
Natural Food ◽  
Rna Seq ◽  
Expression Levels ◽  
Streptomyces Natalensis

Abstract Background Natamycin is a polyene macrolide polyketide antibiotics and used in 150 countries as a natural food preservative. Streptomyces natalensis is an important producer. Elicitation had been approved to be an effective method to improve the biosynthesis of secondary metabolites. Fungal elicitor from Penicillium chrysogenum AS 3.5163 showed inductive effect on the biosynthesis of natamycin in S. natalensis HW-2 fermentation. However, regarding the global gene expression of natamycin in response to fungal elicitor is not still reported. Results RNA-Seq analysis showed that there were 1265 differential expression genes (DEGs) at 40 h and 2196 DEGs at 80 h. The fungal elicitor had stronger effects on the transcription level of S. natalensis HW-2 at 80 h than that at 40 h. Gene Ontology (GO) enrichment analysis of DEGs showed significant enrichment in biological processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the fungal elicitor mainly affected the expression levels of some genes about cellular process, metabolism and genetic information, especially in pentose phosphate pathway (PPP), glycolytic pathway (EMP) and tricarboxylic acid cycle (TCA). KEGG pathway showed that fungal elicitor had a greater influence on the metabolism of branched-chain amino acids (BCAAs). Among them, 23 DEGs associated with BCAAs metabolism were up-regulated or down-regulated. The supplementation experiment with BCAAs confirmed that 0.2 g/L of L-Ile and 0.5 g/L of L-Val increased natamycin yield by 17.6% and 37.8%, respectively. Fungal elicitor also up-regulated the transcriptional levels of most of the enzymes associated with the biosynthesis of natamycin and two important transcription regulators ( pimR and pimM ). To confirm the accuracy of RNA-Seq, the results of qPCR showed that these gene expression levels were in agreement with the transcription changes by RNA-Seq. Conclusion In this study, the change of transcriptional levels in S. natalensis HW-2 under treated with the fungal elicitor was firstly reported. The major finding of our comparative transcriptome analysis is that the fungal elicitor improves the supply of precursor, and alters the expression of natamycin related genes and regulator of secondary metabolism. From our results, we conclude that regulatory alterations are important factors for the enhancement of natamycin.

scholarly journals RCC1 Expression as a Prognostic Marker in Colorectal Liver Oligometastases

2021 ◽  
Vol 27 ◽  
Author(s):  
Yuxiang Deng ◽  
Long Yu ◽  
Yujie Zhao ◽  
Jianhong Peng ◽  
Yanbo Xu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prognostic Marker ◽  
Expression Profiles ◽  
Chromatin Condensation ◽  
Gene Expression Profiles ◽  
Nucleotide Exchange ◽  
Expression Levels ◽  
Independent Prognostic Marker ◽  
Normal Tissues ◽  
Nucleotide Exchange Factor

Introduction: Regulator of chromatin condensation 1 (RCC1) is a major guanine-nucleotide exchange factor for Ran GTPase, and it plays key roles in various biological processes. Previous studies have found that RCC1 may play a role in the development of tumors, but little is known about the relationship between RCC1 and colorectal liver oligometastases (CLOs).Methods: One hundred and twenty-nine pairs of matched human CLO samples, including both primary tumor and its liver metastasis specimens, were subjected to immunohistochemistry to determine the location and expression levels of RCC1. Associations between RCC1 and survival as well as gene expression profiling were explored.Results: In this study, we first observed that RCC1 was mildly increased in CLO tumor tissues compared with normal tissues, and the localization was primarily nuclear. In addition, our study found that high RCC1 expression in liver oligometastases was an independent prognostic marker for unfavorable recurrence-free survival and overall survival (p = 0.036 and p = 0.016). Gene expression profiles generated from microarray analysis showed that RCC1 was involved in pathways including “Myc targets,” “E2F targets” and “DNA repair” pathways.Conclusion: Our data indicated that RCC1 was expressed mainly in the nucleus, and strong and significant associations were found between RCC1 expression levels and the survival of CLO patients. These findings indicated that RCC1 may play a role in CLO development.

scholarly journals OneStopRNAseq: A Web Application for Comprehensive and Efficient Analyses of RNA-Seq Data

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1165 ◽  
Author(s):  
Rui Li ◽  
Kai Hu ◽  
Haibo Liu ◽  
Michael R. Green ◽  
Lihua Julie Zhu
Keyword(s):  
Gene Expression ◽  
Web Application ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Gene Set Enrichment Analysis ◽  
Specific Gene ◽  
Differential Analysis ◽  
Rna Seq ◽  
Data Quality Control ◽  
Private And Public

Over the past decade, a large amount of RNA sequencing (RNA-seq) data were deposited in public repositories, and more are being produced at an unprecedented rate. However, there are few open source tools with point-and-click interfaces that are versatile and offer streamlined comprehensive analysis of RNA-seq datasets. To maximize the capitalization of these vast public resources and facilitate the analysis of RNA-seq data by biologists, we developed a web application called OneStopRNAseq for the one-stop analysis of RNA-seq data. OneStopRNAseq has user-friendly interfaces and offers workflows for common types of RNA-seq data analyses, such as comprehensive data-quality control, differential analysis of gene expression, exon usage, alternative splicing, transposable element expression, allele-specific gene expression quantification, and gene set enrichment analysis. Users only need to select the desired analyses and genome build, and provide a Gene Expression Omnibus (GEO) accession number or Dropbox links to sequence files, alignment files, gene-expression-count tables, or rank files with the corresponding metadata. Our pipeline facilitates the comprehensive and efficient analysis of private and public RNA-seq data.

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