Bioinformatics analysis of key genes associated with the prognosis of breast cancer

Objective:We sought to identify potential therapeutic targets for breast cancer patients by employing a bioinformatics analysis to screen for genes linked with an unfavorable prognosis.Methods:The Gene Expression Omnibus(GEO)database was utilized to obtain three gene expression profile datasets,namely GSE42568,GSE86374,and GSE71053.To identify differentially expressed genes(DEGs),the GEO2R online tool was employed.Subsequently,a func-tional enrichment analysis was conducted.Moreover,a protein-protein interaction network was established using STRING,and DEGs were subjected to module analysis via Cytoscape software to identify pivotal genes.Additionally,the selected pivotal genes underwent further ex-amination and validation utilizing three databases:GEPIA,UALCAN,and Kaplan-Meier Plotter.Results:A total of 121 DEGs were detected,comprising 74 genes with increased expression and 47 genes with decreased expression.Ten key genes were identified:HMMR,RRM2,CDK1,TOP2A,AURKA,CCNB1,MAD2L1,KIF2C,BUB1B,UBE2C.Validation in the GEPIA database revealed high expression levels for all key genes except CDK1.A survival analysis conducted using the Kaplan-Meier Plotter database revealed noteworthy associations between nine crucial genes and the overall survival(OS)of individuals diagnosed with breast cancer.Moreover,these nine key genes exhibited significantly increased expression across different molecular subtypes of breast cancer according to the UALCAN data platform.Conclusions:We identified nine crucial genes significantly linked to the onset,progression,and unfavorable prognosis of breast cancer,providing potential targets for novel treatment options and biomarkers to predict patient outcomes.

Identification of Key Genes in Cotton Fiber

Twenty-eight candidate genes provided by other sub-projects were used to produce transgenic cotton plants.There were over 1000 individuals,and some of them were generation T2 or T3.All

Identification of key genes controlling cancer stem cell characteristics in gastric cancer

BACKGROUND Self-renewal of gastric cancer stem cells(GCSCs)is considered to be the underlying cause of the metastasis,drug resistance,and recurrence of gastric cancer(GC).AIM To characterize the expression of stem cell-related genes in GC.METHODS RNA sequencing results and clinical data for gastric adenoma and adenocarcinoma samples were obtained from The Cancer Genome Atlas database,and the results of the GC mRNA expression-based stemness index(mRNAsi)were analyzed.Weighted gene coexpression network analysis was then used to find modules of interest and their key genes.Survival analysis of key genes was performed using the online tool Kaplan-Meier Plotter,and the online database Oncomine was used to assess the expression of key genes in GC.RESULTS mRNAsi was significantly upregulated in GC tissues compared to normal gastric tissues(P<0.0001).A total of 16 modules were obtained from the gene coexpression network;the brown module was most positively correlated with mRNAsi.Sixteen key genes(BUB1,BUB1 B,NCAPH,KIF14,RACGAP1,RAD54 L,TPX2,KIF15,KIF18 B,CENPF,TTK,KIF4 A,SGOL2,PLK4,XRCC2,a n d C1 orf112)were identified in the brown module.The functional and pathway enrichment analyses showed that the key genes were significantly enriched in the spindle cellular component,the sister chromatid segregation biological process,the motor activity molecular function,and the cell cycle and homologous recombination pathways.Survival analysis and Oncomine analysis revealed that the prognosis of patients with GC and the expression of three genes(RAD54 L,TPX2,and XRCC2)were consistently related.CONCLUSION Sixteen key genes are primarily associated with stem cell self-renewal and cell proliferation characteristics.RAD54 L,TPX2,and XRCC2 are the most likely therapeutic targets for inhibiting the stemness characteristics of GC cells.

Literature-based knowledgebase of pancreatic cancer gene to prioritize the key genes and pathways

Pancreatic cancer （PC） occurs when malignant cells develop in the part of the pancreas, a glandular organ behind the stomach. For 2015, there are about 40,560 people dead of pancreatic cancer （20,710 men and 19,850 women） in the US （Siegel et al., 2015）. Though PC accounts for about 3% of all cancers in the US, it can cause about 7% of cancer deaths. This is mainly because that the early stages of this cancer do not usually produce symptoms, and thus the cancer is almost always fatal when it is diagnosed.

Single-cell RNA-sequencing combined with bulk RNA-sequencing analysis of peripheral blood reveals the characteristics and key immune cell genes of ulcerative colitis

BACKGROUND Ulcerative colitis(UC)is a complicated disease caused by the interaction between genetic and environmental factors that affects mucosal homeostasis and triggers an inappropriate immune response.Single-cell RNA sequencing(scRNA-seq)can be used to rapidly obtain the precise gene expression patterns of thousands of cells in the intestine,analyze the characteristics of cells with the same phenotype,and provide new insights into the growth and development of intestinal organs,the clonal evolution of cells,and immune cell changes.These findings can provide new ideas for the diagnosis and treatment of intestinal diseases.To identify clinical phenotypes and biomarkers that can predict the response of UC patients to specific therapeutic drugs and thus aid the diagnosis and treatment of UC.METHODS Using the Gene Expression Omnibus(GEO)database,we analyzed peripheral blood cell subtypes of patients with UC by scRNA-seq combined with bulk RNA sequencing(RNA-seq)to reveal the core genes of UC.We then combined weighted gene correlation network analysis(WGCNA)and least absolute shrinkage and selection operator(LASSO)analysis to reveal diagnostic markers of UC.RESULTS After processing the scRNA-seq data,we obtained data from approximately 24340 cells and identified 17 cell types.Through intercellular communication analysis,we selected monocyte marker genes as the candidate gene set for the prediction model.Construction of a WGCNA coexpression network identified RhoB,cathepsin D(CTSD)and zyxin(ZYX)as core genes.Immune infiltration analysis showed that these three core genes were strongly correlated with immune cells.Functional enrichment analysis showed that the differentially expressed genes were closely related to immune and inflammatory responses,which are associated with many challenges in the diagnosis and treatment of UC.CONCLUSION Through scRNA-seq analysis,LASSO diagnostic model building and WGCNA,we identified RhoB,CTSD and ZYX as core genes of UC that are closely related to monocyte infiltration that may serve as diagnostic markers and molecular targets for UC therapeutic intervention.

Identification of key pathways and genes from gastric precancerous lesions to gastric cancer by integrated bioinformatics analysis

Objective:This work aimed to illuminate the potential key genes and pathways in GC tumorigenesis based on bioinfOrmatics analysis.Methods:The differentially expressed genes(DEGs)between GPL tissue samples and GC tissue samples were investigated using the GSE55696 and GSE87666 microarray data from the Gene Expression Omnibus(GEO)database.DEGs were identified by an empirical Bayes method based on the Limma R package.Then,KEGG and GO enrichment analyses of DEGs were performed followed by protein-protein interaction(PPI)network construction.Finally,the overall survival(OS)analysis of key genes was performed by the Kaplan-Meier plotter online tool.Results:A total of 250 DEGs were obtained,of which 216 were up-regulated and 34 were down-regulated.KEGG pathways analysis showed that the up-regulated DEGs were enriched in cytokine-cytokine receptor interaction,chemokine signaling pathway,metabolic pathways,PI3K-Akt signaling pathway,NF-kappa B signaling pathway,and other signaling pathways about cancer,while no down-regulated pathways were enriched.A PPI network of DEGs was constructed with 117 nodes and 660 edges,and 20 genes were selected as hub genes owing to high degrees in the network.According to the Kaplan-Meier analysis,6 out of 20 hub genes including CCR7,FPR1,C3,CXCR5,GNB4,and PPBP with high mRNA expression were associated with poor OS for GC patients.Conclusion:The results of this study provide possible factors for the occurrence of GC,and the identification of the genes and pathways associated with the progression from GPL to GC provides valuable data for investigating the pathogenesis in future studies.

Study on conversion of microstates in breast cell ensemble at the gene level based on the eigen-microstate method

Breast cancer is a malignant disease that seriously threatens women's health.Studying the mechanism of cancer occurrence and development is an urgent problem to be solved.In this paper,the eigen-microstate method was used to study conversion of normal breast cells into breast cancer cells and the reason.The main conclusions are as follows:the microstates of normal breast cell and breast cancer cell are different.There is a state conversion when a normal breast cell transforms into a breast cancer cell.The main reason for this state conversion is the combined effect of tumor suppressor genes and oncogenes.By analyzing the function of key genes,it was found that these genes do play an important role in the development of breast cancer.The findings contribute to understanding the mechanism by which breast cancer occurs and progresses,and key genes can serve as potential biomarkers or target genes for breast cancer treatment.

Global gene expression profiling of perirenal brown adipose tissue whitening in goat kids reveals novel genes linked to adipose remodeling

Background Brown adipose tissue(BAT)is known to be capable of non-shivering thermogenesis under cold stimulation,which is related to the mortality of animals.In the previous study,we observed that goat BAT is mainly located around the kidney at birth,and changes to white adipose tissue(WAT)in the perirenal adipose tissue of goats within one month after birth.However,the regulatory factors underlying this change is remain unclear.In this study,we systematically studied the perirenal adipose tissue of goat kids in histological,cytological,and accompanying molecular level changes from 0 to 28 d after birth.Results Our study found a higher mortality rate in winter-born goat kids,with goat birthing data statistics.Then we used thermal imaging revealing high temperature in goat hips at postnatal 0 d and gradually decrease during 28 d.This is consistent with the region of perirenal BAT deposition and highlights its critical role in energy expenditure and body temperature regulation in goat kids.Additionally,we found a series of changes of BAT during the first 28 d after birth,such as whitening,larger lipid droplets,decreased mitochondrial numbers,and down-regulation of key thermogenesis-related genes(UCP1,DIO2,UCP2,CIDEA,PPARGC1a,C/EBPb,and C/EBPa).Then,we used RNA-seq found specific marker genes for goat adipose tissue and identified 12 new marker genes for BAT and 10 new marker genes for WAT of goats.Furthermore,12 candidate genes were found to potentially regulate goat BAT thermogenesis.The mechanism of the change of this biological phenomenon does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.While apoptosis may play a limited role,it is largely not critical in this transition process.Conclusions We concluded that perirenal BAT plays a crucial role in thermoregulation in newborn goat kids,with notable species differences in the expression of adipose tissue marker genes,and we highlighted some potential marker genes for goat BAT and WAT.Additionally,the change from BAT to WAT does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.

Effect of HIV-1 Tat on Secretion of TNF-α and IL-1β by U87 Cells in AIDS Patients with or without AIDS Dementia Complex

Objective To explore the role of HIV-1 tat gene variations in AIDS dementia complex （ADC） pathogenesis. Methods HIV-1 tat genes derived from peripheral spleen and central basal ganglia of an AIDS patient with ADC and an AIDS patient without ADC were cloned for sequence analysis. HIV-1 tat gene sequence alignment was performed by using CLUSTAL W and the phylogentic analysis was conducted by using Neighbor-joining with MEGA4 software. All tat genes were used to construct recombinant retroviral expressing vector MSCV-IRES-GFP/tat. The MSCV-IRES-GFP/tat was cotransfected into 293T cells with pCMV-VSV-G and pUMVC vectors to assemble the recombinant retrovirus. After infection of gliomas U87 cells with equal amount of the recombinant retrovirus, TNF-α, and IL-1β concentrations in the supernatant of U87 cells were determined with ELISA. Results HIV-1 tat genes derived from peripheral spleen and central basal ganglia of the AIDS patient with ADC and the other one without ADC exhibited genetic variations. Tat variations and amino acid mutation sites existed mainly at Tat protein core functional area （38-47aa）. All Tat proteins could induce ug7 cells to produce TNF-α and IL-1β, but the level of IL-1β production was different among Tat proteins derived from the ADC patient＇s spleen, basal ganglia, and the non-ADC patient＇s spleen. The level of Tat proteins derived from the ADC patient＇s spleen, basal ganglia, and the non-ADC patient＇s spleen were obviously higher than that from the non-ADC patient＇s basal ganglia. Conclusion Tat protein core functional area （38-47aa） may serve as the key area of enhancing the secretion of IL-1β. This may be related with the neurotoxicity of HIV-1 Tat.

The Study on BCR/ABL Fusion Gene in Adult Acute Lymphoblastic Leukemia

In order to assess the significance of BCR/ABC fusion gene in adult acute lymphoblastic Leukemia (ALL), 28 patients who were diagnosed as ALL were enrolled to detect BCR/ABC gene using nested-RT-PCR. The results showed that 9 cases (31.25%) were BCR/ABL positive, and expressed P210 subtype. Among them 7 cases were B-ALL, and one was T-ALL. The diagnosis was proved by monoclonal antibodies recognition by indirect immunofluorescence. Adult patients with BCR/ABL positive ALL were significantly older (p<0.01) and had higher WBC count (p<0.01) as compared with BCR/ABL-negative patients. There was no significant difference in sex, hemoglobin and splenomegaly between two group (p>0.05). The induction failure rate was high in BCR/ABL positive patients and those who achieved complete remission usually relapsed earlier. In conclusion, adult ALL patients with BCR/ABL-positive have poorer prognosis.

Rethinking fish biology and biotechnologies in the challenge era for burgeoning genome resources and strengthening food security

Fish biology has been developed for more than 100 years,but some important breakthroughs have been made in the last decade.Early studies commonly concentrated on morphology,phylogenetics,development,growth,reproduction manipulation,and disease control.Recent studies have mostly focused on genetics,molecular biology,genomics,and genome biotechnologies,which have provided a solid foundation for enhancing aquaculture to ensure food security and improving aquatic environments to sustain ecosystem health.Here,we review research advances in five major areas:(1)biological innovations and genomic evolution of four significant fish lineages including non-teleost ray-finned fishes,northern hemisphere sticklebacks,East African cichlid fishes,and East Asian cyprinid fishes;(2)evolutionary fates and consequences of natural polyploid fishes;(3)biological consequences of fish domestication and selection;(4)development and innovation of fish breeding biotechnologies;and(5)applicable approaches and potential of fish genetic breeding biotechnologies.Moreover,five precision breeding biotechniques are examined and discussed in detail including gene editing for the introgression or removal of beneficial or detrimental alleles,use of sex-specific markers for the production of mono-sex populations,controllable primordial germ cell on-off strategy for producing sterile offspring,surrogate broodstock-based strategies to accelerate breeding,and genome incorporation and sexual reproduction regainbased approach to create synthetic polyploids.Based on these scientific and technological advances,we propose a blueprint for genetic improvement and new breed creation for aquaculture species and analyze the potential of these new breeding strategies for improving aquaculture seed industry and strengthening food security.

Mitogen-activated protein kinase signal pathways play an important role in right ventricular hypertrophy of tetralogy of Fallot

Background Tetralogy of Fallot （TOF） is the most common malformation of children with an incidence of approximately 10% of congenital heart disease patients. There can be a wide spectrum to the severity of the anatomic defects, which include ventricular septal defect, aortic override, right ventricular outflow tract obstruction, and right ventricular hypertrophy. We examined the relationship between right ventricular hypertrophy in patients with TOF and the gene expression of factors in the mitogen-activated protein kinase （MAPK） signal pathway. Methods To gain insight into the characteristic gene（s） involved in molecular mechanisms of right ventricular hypertrophy in TOF, differential mRNA and micro RNA expression profiles were assessed using expression-based micro array technology on right ventricular biopsies from young TOF patients who underwent primary correction and on normal heart tissue. We then analyzed the gene expression of the MAPK signal pathway using reverse transcription-polymerase chain reaction （RT-PCR） in normals and TOF patients. Results Using the micro RNA chip V3.0 and human whole genome oligonucleotide microarray VI.0 to detect the gene expression, we found 1068 genes showing altered expression of at least two-fold in TOF patients compared to the normal hearts, and 47 micro RNAs that showed a significant difference of at least two-fold in TOF patients. We then analyzed these mRNAs and micro RNAs by target gene predicting software Microcosm Targets version 5.0, and determined those mRNA highly relevant to the right ventricular hypertrophy by RT-PCR method. There were obvious differences in the gene expression of factors in the MAPK signal pathway when using RT-PCR, which was consistent to the results of the cDNA microarray.Conclusion The upregulation of genes in the MAPK signal pathway may be the key events that contribute to right ventricular hypertrophy and stunted angiogenesis in patients with TOF.