Identification and validation of a new prognostic signature based on cancer-associated fibroblast-driven genes in breast cancer

BACKGROUND Breast cancer(BC),a leading malignant disease,affects women all over the world.Cancer associated fibroblasts(CAFs)stimulate epithelial-mesenchymal transition,and induce chemoresistance and immunosuppression.AIM To establish a CAFs-associated prognostic signature to improve BC patient out-come estimation.METHODS We retrieved the transcript profile and clinical data of 1072 BC samples from The Cancer Genome Atlas(TCGA)databases,and 3661 BC samples from the The Gene Expression Omnibus.CAFs and immune cell infiltrations were quantified using CIBERSORT algorithm.CAF-associated gene identification was done by weighted gene co-expression network analysis.A CAF risk signature was established via univariate,least absolute shrinkage and selection operator regression,and mul-tivariate Cox regression analyses.The receiver operating characteristic(ROC)and Kaplan-Meier curves were employed to evaluate the predictability of the model.Subsequently,a nomogram was developed with the risk score and patient clinical signature.Using Spearman's correlations analysis,the relationship between CAF risk score and gene set enrichment scores were examined.Patient samples were collected to validate gene expression by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS Employing an 8-gene(IL18,MYD88,GLIPR1,TNN,BHLHE41,DNAJB5,FKBP14,and XG)signature,we attemp-ted to estimate BC patient prognosis.Based on our analysis,high-risk patients exhibited worse outcomes than low-risk patients.Multivariate analysis revealed the risk score as an independent indicator of BC patient prognosis.ROC analysis exhibited satisfactory nomogram predictability.The area under the curve showed 0.805 at 3 years,and 0.801 at 5 years in the TCGA cohort.We also demonstrated that a reduced CAF risk score was strongly associated with enhanced chemotherapeutic outcomes.CAF risk score was significantly correlated with most hallmark gene sets.Finally,the prognostic signature were further validated by qRT-PCR.CONCLUSION We introduced a newly-discovered CAFs-associated gene signature,which can be employed to estimate BC patient outcomes conveniently and accurately.

Distribution of gene polymorphisms associated with aspirin antiplatelet in the Han NSTEMI population

Objective:To analyze the genotype and allele distribution characteristics of GPⅢa PLA2(rs5918),PEAR1(rs12041331),and PTGS1(rs10306114)genes related to the antiplatelet pharmacological effects of aspirin,providing reference for individualized treatment of Chinese Han NSTEMI patients.Methods:A total of 107 Han patients with NSTEMI in Beijing Luhe Hospital affiliated to Capital Medical University from January 2016 to December 2022 were selected as the research subjects.The genotypes of GPⅢa PLA2(rs5918),PEAR1(rs12041331)and PTGS1(rs10306114)were detected by fluorescence staining in situ hybridization.The frequency distribution and allele distribution of genotype were analyzed.The results were analyzed whether there were statistical differences in the distribution of related alleles between the Han NSTEMI population and some populations in the 1000 Genomes database.Results:In the Han NSTEMI population,the genotype frequencies of GPⅢa PLA2(rs5918)locus were TT 97.20%,TC 2.80%and CC 0%,the allele frequencies were T 98.60%and C 1.40%.The genotype frequencies of PEAR1(rs12041331)locus were GG 42.06%,GA 44.86%and AA 13.08%,the allele frequencies were G 64.49%and A 35.51%.The genotypes at the PTGS1(rs10306114)locus were all AA(100%),no AG or GG genotype was found.Conclusion:In the NSTEMI population of Han nationality,the mutation at GPⅢa PLA2(rs5918)site related to aspirin antiplatelet pharmacology is rare,and there is no mutation at PTGS1(rs10306114)site.Wild homozygotes are dominant in these two gene loci,while mutations in PEAR1(rs12041331)are more common.Some of the findings in this study are similar to those in previous reports or other populations included in the relevant database;however,some results differ from previous reports or other populations。

Association between 5-HTR1A gene C-1019G polymorphism and antidepressant response in patients with major depressive disorder:A meta-analysis

BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify the impact of genetic variation on MDD treatment outcomes.METHODS Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,a systematic search across PubMed,EMBASE,Web of Science,and the Cochrane Library was conducted without date restrictions,utilizing key terms related to MDD,serotonin 1A receptor polymorphism(5-HTR1A),C-1019G polymorphism,and antidepressant response.Studies meeting inclusion criteria were thoroughly screened,and quality assessed using the Newcastle-Ottawa Scale.Statistical analyses,includingχ2 and I²values,were used to evaluate heterogeneity and fixed-effect or random-effect models were applied accordingly.RESULTS The initial search yielded 1216 articles,with 11 studies meeting criteria for inclusion.Analysis of various genetic models showed no significant association between the 5-HTR1A C-1019G polymorphism and antidepressant efficacy.The heterogeneity was low to moderate,and no publication bias was detected through funnel plot symmetry and Egger's and Begg's tests.CONCLUSION This meta-analysis does not support a significant association between the 5-HTR1A C-1019G polymorphism and the efficacy of antidepressant treatment in MDD.The findings call for further research with larger cohorts to substantiate these results and enhance the understanding of antidepressant pharmacogenetics.

Polymorphisms in base excision repair genes: Breast cancer risk and individual radiosensitivity

Breast cancer(BC) is the most common cancer among women worldwide. The aetiology and carcinogenesis of BC are not clearly defined, although genetic, hormonal, lifestyle and environmental risk factors have been established. The most common treatment for BC includes breast-conserving surgery followed by a standard radiotherapy(RT) regimen. However, radiation hypersensitivity and the occurrence of RT-induced toxicity in normal tissue may affect patients' treatment. The role of DNA repair in cancer has been extensively investigated, and an impaired DNA damage response may increase the risk of BC and individual radiosensitivity. Single nucleotide polymorphisms(SNPs) in DNA repair genes may alter protein function and modulate DNA repair efficiency, influencing the development of various cancers, including BC. SNPs in DNA repair genes have also been studied as potential predictive factors for the risk of RT-induced side effects. Here, we review the literature on the association between SNPs in base excision repair(BER) genes and BC risk. We focusedon X-ray repair cross complementing group 1(XRCC1), which plays a key role in BER, and on 8-oxoguanine DNA glycosylase 1, apurinic/apyrimidinic endonuclease 1 and poly(ADP-ribose) polymerase-1, which encode three important BER enzymes that interact with XRCC1. Although no association between SNPs and radiation toxicity has been validated thus far, we also report published studies on XRCC1 SNPs and variants in other BER genes and RT-induced side effects in BC patients, emphasising that large well-designed studies are needed to determine the genetic components of individual radiosensitivity.

Polymorphisms at <i>GSTM </i>1, <i>GSTP </i>1, <i>GSTT </i>1 Detoxification Genes Loci and Risk of Breast Cancer in Kazakhstan Population

Associations of null polymorphism (copy number variation) of detoxification genes GSTM1, GSTT1 and GSTP1 (at rs2495636, 105 Ile/Val) with the breast cancer (BC) were assessed in two main ethnic groups of the Republic of Kazakhstan (Kazakhs and Russians). Total number of patients was 181, and of controls 397. Statistically significant difference was observed between BC patients and healthy individuals in alleles frequency (χ2 = 4.89, р = 0.007) of GSTP1 gene at rs2495636 (105 Ile/Val) among the Kazakhs ethnic group. Difference in genotypes distribution (χ2 =5.26, р = 0.076) at this site is approximating to be statistically significant. In the Russian group, no differences were found in genotypes and alleles atrs 2495636 of GSTP1 gene between cases and controls. There was no significant difference between null polymorphism (copy number variation) of GSTM1 and GSTT1 genes among cases and controls in both ethnic groups.

Associations of Polymorphisms of the <i>CYP</i>1<i>A</i>1 and <i>CYP</i>1<i>B</i>1 Cytochrome P450 Genes with Breast Cancer in Kazakhstan

Associations of polymorphisms in rs4646903 site of CYP1A1 and rs1056836 site of CYP1B1 genes with the breast cancer (BC) were studied in two main ethnic groups of Kazakhstan Republic (Kazakhs and Russians). Total number of BC patients was 181, controls—397. The statistically significant differences were revealed in allele frequencies (χ2 = 5.93, р = 0.004) and in genotypes distribution (χ2 = 8.71, р = 0.015) in rs4646903 site of CYP1A1 gene in Kazakh but not in Russian group. The study of CYP1В1 rs1056836 site demonstrated differences in genotype distributions (χ2 = 7.48, р = 0.023) between BC patients and controls in Russian but not in Kazakh ethnic group.

Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria

BACKGROUND Diabetic kidney disease is one of the common complications of type 2 diabetes(T2D).There are no typical symptoms in the early stage,and the disease will progress to moderate and late stage when albuminuria reaches a high level.Treatment is difficult and the prognosis is poor.At present,the pathogenesis of diabetic kidney disease is still unclear,and it is believed that it is associated with genetic and environmental factors.AIM To explore the relationship between the glucokinase regulatory protein(GCKR)gene rs780094 polymorphism and T2D with albuminuria.METHODS We selected 252 patients(126 males and 126 females)with T2D admitted to our hospital from January 2020 to October 2020,and 66 healthy people(44 females and 22 males).According to the urinary albumin/creatinine ratio,the subjects were divided into group I(control),group II(T2D with normoalbuminuria),group III(T2D with microalbuminuria),and group IV(T2D with macroalbuminuria).Additionly,the subjects were divided into group M(normal group)or group N(albuminuria group)according to whether they developed albuminuria.We detected the GCKR gene rs780094 polymorphism(C/T)of all subjects,and measured the correlation between GCKR gene rs780094 polymorphism(C/T)and T2D with albuminuria.RESULTS Gene distribution and genotype distribution among groups I-IV accorded with the Hardy-Weinberg equilibrium.Genotype frequency was significantly different among the four groups (P = 0.048, χ^(2)= 7.906). T allele frequency in groups II, III, and IV was significantly higherthan that in group I. Logistic regression analysis of the risk factors for T2D with albuminuria showed that the CT +TT genotype (odds ratio = 1.710, 95% confidence interval: 1.172-2.493) was a risk factor.CONCLUSION CT + TT genotype is a risk factor for T2D with albuminuria. In the future, we can assess the risk of individualscarrying susceptible genes to delay the onset of T2D.

Analysis of Genetic Alterations in TP53 Gene in Breast Cancer - A Secondary Publication

Tumor protein p53 (TP53) mediates DNA repair and cell proliferation in growing cells. The TP53 gene is a tumor suppressor that regulates the expression of target genes in response to multiple cellular stress factors. Key target genes are involved in crucial cellular events such as DNA repair, cell cycle regulation, apoptosis, metabolism, and senescence. TP53 genetic variants and the activity of the wild-type p53 protein (WT-p53) have been linked to a wide range of tumorigenesis. Various genetic and epigenetic alterations, including germline and somatic mutations, loss of heterozygosity, and DNA methylation, can alter TP53 activity, potentially resulting in cancer initiation and progression. This study was designed to screen three reported mutations in the DNA-binding domain of the p53 protein in breast cancer, to evaluate the relative susceptibility and risk associated with breast cancer in the local population. Genomic DNA was isolated from 30 breast tumor tissues along with controls. Tetra and Tri ARMS PCR were performed to detect mutations in the TP53 coding region. For SNPs c.637C>T and c.733C>T, all analyzed cases were homozygous for the wild-type allele ‘C,’ while for SNP c.745A>G, all cases were homozygous for the wild-type allele ‘A.’ These results indicate no relevance of these three SNPs to cancer progression in our study cohort. Additionally, the findings from whole exon sequencing will help to predict more precise outcomes and assess the importance of TP53 gene mutations in breast cancer patients.

Correlation between Toll-like Receptor Gene Polymorphisms and Idiopathic Nephrotic Syndrome in Chinese Children

Objective Idiopathic nephrotic syndrome(INS)is the most common glomerular disease in children.Toll-like receptors(TLRs)have been reported to be associated with response to steroid treatment in children with INS.Nevertheless,the correlation between TLR genes and the progression of INS has not yet been clarified.The present study aimed to investigate the association of single-nucleotide polymorphisms(SNPs)in TLR2,TLR4,and TLR9 with susceptibility to INS as well as the clinical phenotyping of steroid responsiveness in Chinese children with INS.Methods A total of 183 pediatric inpatients with INS were included and given standard steroid therapy.Based on their clinical response to steroids,the patients were classified into three groups:steroid-sensitive nephrotic syndrome(SSNS),steroid-dependent nephrotic syndrome(SDNS),and steroid-resistant nephrotic syndrome(SRNS).A total of 100 healthy children were employed as controls.The blood genome DNA was extracted from each participant.Six SNPs(rs11536889,rs1927914,rs7869402,rs11536891,rs352140,and rs3804099)in TLR2,TLR4,and TLR9 were selected and detected by multiplex polymerase chain reaction with next-generation sequencing to assess TLR gene polymorphisms.Results Among the 183 patients with INS,89(48.6%)had SSNS,73(39.9%)had SDNS,and 21(11.5%)had SRNS.No significant difference was found in the genotype distribution between healthy children and patients with INS.However,the genotype and allele frequencies of TLR4 rs7869402 were significantly different between SRNS and SSNS.Compared with patients with the C allele and CC genotype,patients with the T allele and CT genotype had an increased risk of SRNS.Conclusion TLR4 rs7869402 affected the steroid response in Chinese children with INS.It might be a predictor for the early detection of SRNS in this population.

Maternal TMPRSS6 Gene Polymorphism rs855791SNP in Women with Preeclampsia

Introduction: Preeclampsia can lead to several maternal and perinatal adverse effects. There are few published data on the association between transmembrane serine protease 6 (TMPRSS6) gene polymorphism and preeclampsia. Objective: To assess the association between TMPRSS6 gene polymorphism rs855791SNP in women with preeclampsia compared with healthy pregnant women. Method: A case-control study (60 women in each arm) was conducted at Saad Abuaela Maternity Hospital in Khartoum, Sudan. Sociodemographic and clinical data were gathered through a questionnaire. The participant was genotype for TMPRSS6 gene rs855791SNP using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP). The results were confirmed by DNA sequencing. Result: There was no significant difference in the median of age, parity, and body mass index. The distribution of the genotypes and alleles of TMPRSS6 rs855791 was consistent with the HWE. The overall TMPRSS6 rs855791 polymorphism was not significantly associated with preeclampsia. However, the proportion of heterozygotes (TC) was considerably higher in the women with preeclampsia (46.7%) than in the control group (23.3%) (p = 0.001;OR = 2.71;95% CI = 1.21 - 6.07). The proportion of homozygotes (TT) and T alleles was not significantly different between women with preeclampsia and the control group. Conclusion: The overall TMPRSS6 rs855791 polymorphism was not significantly associated with preeclampsia and healthy control.

Association of Host Interferon-γ Gene Polymorphism with Toxoplasma gondii Infection in Pregnant Women of Bangladesh

Human toxoplasmosis is caused by the intracellular protozoan parasite Toxoplasma gondii. Although T. gondii infection is generally asymptomatic for most of the immunocompetent adults, severe complications may occur particularly in pregnant women and immunocompromised individual. Host cell immunity plays a critical role in parasite differentiation and persistence in the host. Therefore, genetic polymorphism in the host immune genes, for instance interferon-γ gene could be linked with possibility of T. gondii infection. The objective of the study was to verify the link between the single nucleotide polymorphisms (SNPs) in the IFN-γ gene of pregnant women and T. gondii infection through correlating with anthropometric and sociodemographic parameters. In this study, ninety-two (N = 92) pregnant women (16 - 40 years) and healthy controls (N = 95) with similar age ranges were included. Among them, 25% (n = 23) pregnant women were seropositive for T. gondii IgG antibodies by Rapid Test Assay. Allelic and genotypic frequencies of IFN-γ +874T/A (rs2430561) SNPs were evaluated by using ARMS-PCR. The distribution of the A and T alleles in the specific position of the IFN-γ gene in the T. gondii-infected pregnant women and the control groups did not differ significantly, according to the data. However, we found a higher frequency (13.04%) of A/A genotype in T. gondii infected pregnant women as compared to non-infected individuals (8.70%), demonstrating that T. gondii infection susceptibility may be increased by homozygosity for the A allele. Further studies are to be needed to find out the link between host gene polymorphism and T. gondii infection in Bangladesh.

Correlation between MCP-1 gene-2518A/G polymorphism and diabetic retinopathy: A meta-analysis

Objective:To systematically evaluate the association between MCP-1 gene-2518 A/G polymorphism and diabetic retinopathy(DR).Methods:CNKI,WanFang Data,and PubMed databases were searched.Studies on the correlation between MCP-1 gene-2518A/G polymorphism and DR were searched from self-built databases until March 2022.Meta-analysis was performed using Revman5.3 software.Results:Seven studies were included.Meta-analysis showed that MCP-1 gene 2518A/G was not associated with the risk of DR in allelic and homozygous genetic models[G vs.A:OR=1.09,95%CI(0.77,1.54),P=0.62;GG vs.AA:OR=1.64,95%CI(0.93,2.88),P=0.09],and it was correlated with the risk of DR in heterozygous,dominant and recessive genetic models[GG vs.AG:OR=1.13,95%CI(1.01,1.26),P=0.03;AA+AG vs.GG:OR=0.85,95%CI(0.77,0.94),P=0.002;AA vs.GG+AG:[OR=0.78,95%CI(0.67,0.90),P=0.0008];According to the severity of DR,further meta-analysis of proliferative diabetic retinopathy(PDR)and nonproliferative diabetic retinopathy(NPDR)patients showed that there was no correlation between MCP-1 gene-2518A/G polymorphism and the risk of PDR in five genetic models[G vs.A:OR=1.06,95%CI(0.80,1.41),P=0.68;GG vs.AA:OR=1.12,95%CI(0.77,1.61),P=0.56;GG vs.AG:OR=0.88,95%CI(0.69,1.12),P=0.31;AA+AG vs.GG:OR=1.08,95%CI(0.86,1.36),P=0.50;AA vs.GG+AG:[OR=0.73,95%CI(0.49,1.08),P=0.12].Conclusion:MCP-1 gene 2518A/G polymorphism may be associated with the pathogenesis of DR,but it may not be involved in the progression of DR patients from NPDR to PDR.

Bioinformatics screening of breast cancer-related genes and potential drug research

Objective:To search the the differentially expressed genes between breast cell carcinoma tissues and normal tissues by using bioinformatics technology,and the potential therapeutic drugs for breast cancer were identified,which can provide reference for clinical immune targeted therapy and drug therapy of breast cancer in the future.Methods:"Breast cancer"was searched by using Gene Expression Omnibus(GEO),and GSE79586 chip data was downloaded.The differentially expressed genes in the control group and the breast cancer model group were screened by using bio-communication technology and subjected to GO function analysis,KEGG pathway analysis,differential gene characteristic expression analysis and protein-protein interaction network(PPI)analysis,and the analysis results were further visualized.Prognosis analysis,related function prediction and immune infiltration analysis were performed using the GEPIA,GeneMANIA,and Timer2.0 databases,respectively.Finally,the compounds with potential therapeutic effects on breast cancer are identified through Connectivity Map(CMap).Western blotting and real-time PCR(RT-PCR)were used to verify the core genes and potential therapeutic agents with the highest correlation in vitro.Results:A total of 3916 differentially expressed genes including 1786 up-regulated genes and 2130 down-regulated genes were screened.GO analysis showed that the differential genes were mainly involved in the positive regulation of phosphorylation,secretory vesicles,racemase and epimerase activities.KEGG analysis showed that differential genes were involved in systemic lupus erythematosus,alcoholism,sticky spots,amoebic dysentery Ras signal pathways and other disease pathways.The characteristic expression analysis of differential genes showed that MEK inhibitors,HSP90 inhibitors and signal transduction pathway kinase inhibitors were drugs similar to the differential genes.PPI results showed that H2AFJ,TFF1,GATA3,FOXA1,and CDH1 were core genes related to breast cancer.Two core genes of H2AFJ and TFF1 with the highest correlation were further selected for GEPIA analysis.The results of the analysis showed that the mRNA expression levels of H2AFJ and TFF1 in breast cancer cells were significantly higher than those in normal tissues,and there was a significant correlation with the pathological staging,overall survival rate and disease-free survival rate of breast cancer patients.H2AFJ and TFF1 may be potential prognostic biomarkers for survival of breast cancer patients.The functions of differentially expressed H2AFJ and TFF1 are mainly related to hormone receptor binding,epithelial structure maintenance and epigenetic negative regulation of genes,chromatin tissue involved in negative regulation of transcription,etc.The results of immune infiltration showed that the expressions of H2AFJ and TFF1 had a significant correlation with the infiltration of macrophages,neutrophils,monocytes,CD4+T,CD8+T,B lymphocytes and other immune cells.CMap results showed that compounds such as Gefitinib,Alpelisib,Sorafenib,and Sunitinib had potential therapeutic effects on breast cancer.Western blot and RT-PCR results showed that H2AFJ and TFF1 were significantly overexpressed in breast cancer cells.Gefitinib significantly inhibited the expression of H2AFJ and TFF1 in breast cancer cells(P<0.05,P<0.01).Conclusion:In this study,differentially expressed genes between breast cell carcinoma tissues and normal tissues were screened out by bioinformatics means to further identify key genes and compounds with potential therapeutic effects in the onset process of breast cancer and to further verify the effectiveness of the screened drugs on breast cancer through experiments.It will provide reference for clinical research and development of new drugs against breast cancer in the future in order to develop more effective treatment options.

Roles of the Apolipoprotein E Gene and Its Polymorphisms in the Etiopathophysiology of Type 2 Diabetes Mellitus and Its Atherosclerotic Complication in Senegalese Females

Lipid metabolism disorders would be among the components responsible for the risk of the onset of T2DM and its vascular complications. Apolipoprotein E plays an important role in lipid metabolism. We studied the involvement of the APOE gene in the onset of T2DM and its vascular complications. Clinical and biochemical parameters were assessed in each participant. APOE genotypes were identified by PCR-RFLP. Arterial stiffness was studied using a pOpmetre® which evaluates the pulse wave velocity (ft-PWV). Endothelial dysfunction was studied using an EndoPAT2000® which measures endothelium-dependent vasodilation (RHI). In control subjects, the ε3 allele was associated with an increase in fasting blood glucose (r = 2.36, p = 0.018), and a decrease in LDL cholesterol levels (r = −2.17, p = 0.03), and ε4 was associated with an increase in total cholesterol (r = 2.59, p = 0.01), LDL cholesterol (r = 2.84, p = 0.004), and No-HDL cholesterol (r = 2.74, p = 0.006). In type 2 diabetes subjects, the ε2 was associated with a decrease in diastolic blood pressure (r = −2.25, p = 0.02). The ε3 was associated with a decrease in ft-PWV (r = −2.26, p = 0.024) while the ε4 was associated with an increase in ft-PWV (r = 2.52, p = 0.012). Carrying the ε2ε3 genotype would have in 99% a limited risk of developing T2DM, and in event of T2DM, only 1 to 2% would have a significant risk of developing atherosclerosis, which would be severe in 17%. Of the ε2ε4 genotype, 93% had a limited or even possible risk of developing T2DM, the remaining 7% had a very high risk of developing T2DM. Diabetics carrying ε2ε4 had in 7% very high risk of developing atherosclerosis. The latter had a 20% very high risk of being very severe. Subjects carrying the ε3ε4 genotype had a 67% possible or even probable risk of developing T2DM and in the event of diabetes, there was in 34% very high risk of developing atherosclerosis which will not have even the time to evolve towards severity. For subjects carrying the ε3ε3, the risk of developing T2DM and athérosclerosis was higher than that of the ε2ε3, and ε2ε4 genotypes but lower than that ε3ε4 genotype. The physio-pathological role of the APOE gene and the impacts of its polymorphisms are important in the onset and progression of type 2 diabetes mellitus.

Glutamate decarboxylase 1 gene polymorphisms are associated with respiratory symptoms in panic disorder

BACKGROUND Genetic factors play an important role in the pathogenesis of panic disorder(PD).However,the effect of genetic variants on PD remains controversial.AIM To evaluate the associations between glutamate decarboxylase 1(GAD1)gene polymorphisms and PD risk and assess the effect of GAD1 gene polymorphisms on the severity of clinical symptoms in PD.METHODS We recruited 230 PD patients and 224 healthy controls in this study.All participants were assessed for anxiety and panic symptom severity using the Hamilton Anxiety Rating Scale(HAM-A)and Panic Disorder Severity Scale(PDSS).GAD1 gene polymorphisms(rs1978340 and rs3749034)were genotyped and assessed for allele frequencies.RESULTS There were no significant differences between cases and controls in the genotype distributions or allele frequencies of GAD1(rs1978340 and rs3749034).In addition,the effect of GAD1(rs1978340 and rs3749034)on PD severity was not significant.However,regarding respiratory symptoms,patients with the GAD1 rs1978340 A/A genotype had significantly higher scores than those with the A/G or G/G genotype.CONCLUSION Here,we showed that the A/A genotype of GAD1 rs1978340 was associated with increased severity of respiratory symptoms in patients with PD.

The moderating role of NTSR1 polymorphisms on personality and coping styles among breast cancer patients

Background:Some personality traits could be a predictor for coping styles.The objective of this investigation was to examine the correlation between personality traits and coping mechanisms in the context of gene regulation among breast cancer patients.Material and methods:This cross-sectional study was performed in 2021.A total of 200 breast cancer patients were included in this study.Data were collected using the Trait Coping Style Questionnaire(TCSQ)and the Eysenck Personality Questionnaire-Revised Short Scale for Chinese(EPQ-RSC).And individuals’blood was tested for genotype.Results:The findings indicated that there existed an inverse relationship between extraversion and negative coping style while also demonstrating a significant association between extraversion and positive coping style.Neuroticism was positively correlated with negative coping style but negatively with positive coping style.The SNP of NTSR1 only moderated the relationship between neuroticism and negative coping styles in breast cancer patients.Conclusion:The present investigation delves into the correlation between personality traits and coping mechanisms at the molecular level in breast cancer patients.

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.

Role of polymorphisms in genes that encode cytokines and Helicobacter pylori virulence factors in gastric carcinogenesis

The Helicobacter pylori(H. pylori) infection is a determinant factor in gastric cancer(GC) development. However, the infection outcomes are variable and depend on both host and bacterial characteristics. Some host cytokines such as interleukin(IL)-1β, IL-1 Ra, IL-8, IL-10 and tumor necrosis factor-α play important roles in the host immune system response to the pathogen, in the development of gastric mucosal lesions and in cell malignant transformation. Therefore, these host factors are crucial in neoplastic processes. Certain polymorphisms in genes that encode these cytokines have been associated with an increased risk of GC. On the other hand, various virulence factors found in distinct H. pylori bacterial strains, including cytotoxinassociated antigen A, vacuolating cytotoxin, duodenal ulcer promoting gene A protein, outer inflammatory protein and blood group antigen binding adhesin, have been associated with the pathogenesis of different gastric diseases. The virulent factors mentioned above allow the successful infection by the bacterium and play crucial roles in gastric mucosa lesions, including malignant transformation. Moreover, the role of host polymorphisms and bacterial virulence factors in gastric carcinogenesis seems to vary among different countries and populations. The identification of host and bacterium factors that are associated with an increased risk of GC development may be useful in determining the prognosis of infection in patients, what could help in clinical decision-making and in providing of an optimized clinical approach.

Association of polymorphisms of IL and CD14 genes with acute severe pancreatitis and septic shock

AIM. To investigate IL-1β＋3 594 in the 5^th intron, IL-10-1 082 and CD14-159 polymorphisms in patients with acute pancreatitis （AP） and septic shock.METHODS： The study induded 215 patients （109 with acute severe pancreatitis （SAP）, 106 with acute mild pancreatitis （MAP）） and 116 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients and healthy controls using restriction fragment length polymorphism analysis of PCR products.RESULTS： The frequencies of IL-β＋3 594T, IL-10-1082G and CD14-159T allele were similar in patients with mild or severe pancreatitis and in controls. Within SAP patients, no significant differences were found in the allele distribution examined when etiology was studied again. Patients with septic shock showed a significantly higher prevalence of IL-10-1082G allele than those without shock （X^2 = 5.921,P= 0.015）.CONCLUSION： IL-10-1082G plays an important role in the susceptibility of SAP patients to septic shock. Genetic factors are not important in determination of disease severity or susceptibility to AP.

A case-control study about the association between vascular endothelial growth inhibitor gene polymorphisms and breast cancer risk in female patients in Northeast China

Objective： The inhibition of the neovascularization in tumors is a potential therapeutic target of cancer. Vascular endothelial growth inhibitor （VEGI） is a member of the TNF superfamily which has the ability to suppress the formation of new vessels in tumors. In order to study the association between VEGI gene polymorphisms and breast cancer risk, a case-control study was conducted in Chinese Han women in Northeast China. Methods： Our study involved 708 female breast cancer patients and 685 healthy volunteers. Four SNPs of VEGI gene were analyzed through the polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） method. The association between VEGI gene polymorphisms and breast cancer risk was analyzed in our study. The relation between VEGI gene variants and clinical features of breast cancer including lymph node （LN） metastasis, esl^ogen receptor （ER）, progestrogen receptor （PR）, tumor protein 53 （1953）, human epidermal growth factor receptor 2 （Her-2） and triple negative （ER-/PR-/Her-2-） status was analyzed as well. Results： We found that the CT genotype and T allele of rs6478106 were more frequent in patients than in controls. There was also a statistical difference in the distribution of Crs6478106Grs4263839 haplotype between patients and controls. In addition, SNP rs6478106 and rs4979462 were related with the Her-2 status. Conclusions： Our results suggest that VEGI gene variants may be related to the breast cancer risk and the clinical features of breast cancer in Chinese Han women in Northeast China.