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Identification of broad-spectrum B-cell and T-cell epitopes of H9 subtype avian influenza virus HA protein using polypeptide scanning 认领 引用
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作者 Keji Quan Nan Zhang +10 位作者 Mengqi Lin Yuan Liu Yue Li Qun Hu Maoshun Nie Tao Qin Jingzhi Li Hongwei Ma Sujuan Chen Daxin Peng Xiufan Liu 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2026年第4期1636-1646,共11页
The H9N2 subtype avian influenza virus(AIV)hemagglutinin(HA)protein is a major immunogen in which HA1 is a genetic variant and HA2 is relatively conserved.Identifying broad-spectrum antigen epitopes targeting HA1 is c... The H9N2 subtype avian influenza virus(AIV)hemagglutinin(HA)protein is a major immunogen in which HA1 is a genetic variant and HA2 is relatively conserved.Identifying broad-spectrum antigen epitopes targeting HA1 is crucial for vaccine design and detection.Based on the phylogenetic and serological analyses,we identified 2 antigenic groups and 3 representative viruses:A/chicken/Jiangsu/JY040218C/2019,A/pigeon/Jiangsu/JY020616/2019,and A/chicken/Jiangsu/WX090312/2018.An overlapping peptide library was synthesized using HA1 amino acid sequences of the viruses as templates.Through peptide scanning of the sera against different strains of H9N2 subtype AIV,we identified peptides from 4 regions(H9-2/3,H9-20/21,H9-26,and H9-29/30/31)that demonstrated broad-spectrum reactivity.Immunological assay results demonstrated that H9-21(219RIFKPLIGPRPLVNGLMGRI239),H9-26(269SGESHGRILKTDLKMGSCTV289),and H9-30(309YAFGNCPKYI GVKSLKLAVG329)effectively induced antibody generation and conferred partial protective efficacy against the parent virus JY040218C.The results of lymphocyte proliferation and ELISpot assays indicated that peptides H9-15(159MRWLTQKNNAYPTQDAQYTN179),H9-22(229PLVNGLMGRINYYWSVLKP G249),and H9-23(239NYYWSVLKPGQTLRIKSDGN259)could effectively stimulate the expression of interferon-gamma in peripheral blood lymphocytes of chickens immunized against different strains of H9N2 AIV.Collectively,5 novel cell epitopes H9-15,H9-22,H9-23,H9-26,and H9-30,including the best B cell epitope H9-26 and the best T cells epitope H9-22,were identified that could be targeted for vaccine design or detection approaches against H9N2 AIVs. 展开更多
关键词 H9N2 subtype avian influenza virus HA protein epitope microarray peptide
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Mutational signature-based classification uncovers emerging oral cancer subtypes with distinct molecular patterns 认领 引用
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作者 Sophie Deneuve Béatrice Fervers +17 位作者 Julia SBruno Emma Bach Sergey Senkin Gabrielle Goldman-Lévy Christine Carreira Israa Laklouk Rong Hu Liacine Bouaoun Olivia Pérol Bérénice Chavanel Lingeng Lu Taja Lozar Tarik Gheit Paul FLambert Isabelle Coste Toufic Renno Jiri Zavadil François Virard 《International Journal of Oral Science》 SCIE CAS CSCD 2026年第3期401-415,共15页
Tobacco use,alcohol consumption,and infection with human papilloma virus(HPV)are well-established risk factors for head and neck squamous cell carcinomas(HNSCC).However,the incidence of oral cancer,particularly in the... Tobacco use,alcohol consumption,and infection with human papilloma virus(HPV)are well-established risk factors for head and neck squamous cell carcinomas(HNSCC).However,the incidence of oral cancer,particularly in the mobile tongue,has been rising in non-smokeron-drinker and HPV-negative patients,suggesting the emergence of a new clinical entity.To understand in molecular terms this subtype of oral cavity squamous cell carcinomas(OCSCC)with no-identified risk factor(NIRF),we analyzed the available public head and neck cancer multi-omics data.We identified mutational signatures that stratified 253 OCSCC and 94 laryngeal cancer cases,used as tobacco-only-related controls,according to their clinico-pathological characteristics.We show that tobacco,depending on the anatomical site,triggers distinct mutational processes and further demonstrate that the single-basesubstitution(SBS)signature SBS16 in OCSCC is associated with tobacco smoking,reflecting the combined effects of smoking and drinking.Importantly,we identified a tongue cancer-enriched NIRF OCSCC subgroup exhibiting significantly increased endogenous clock-like mutagenesis,while another NIRF subgroup manifested with elevated apolipoprotein B mRNA editing enzyme catalytic polypeptide-like(APOBEC)-associated mutagenesis.Both NIRF OCSCC subgroups harbored specific cancer driver mutations and distinct methylation patterns,which differed from those observed in OCSCC linked to traditional HNSCC risk factors,reflecting unique molecular programs underlying disease development.Specifically,NIRF-OSCC exhibited pronounced immune evasion strategies and antimicrobial transcriptomic responses.Our study presents the first molecular and genomic characterization of the emerging NIRF OCSCC subtype likely driven by increased endogenous mutagenesis and responses to microbial insults.These findings warrant future detailed investigations into etiology and have implications for clinical management and cancer prevention. 展开更多
关键词 human papilloma virus hpv oral cancerparticularly non smoker non drinker oral cavity squamous cell carcinomas ocscc emerging subtype head neck squamous cell carcinomas hnscc howeverthe HPV negative oral cancer
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Integrative multi-omics clustering for identifying novel breast cancer subtypes with distinct molecular and clinical characteristics 认领 引用
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作者 Tao Wang Liuxian Wu +5 位作者 Yuzhe Gao Huan Chen Zehua Dai Tao Chen Xiaochong Deng Jing Hou 《Intelligent Oncology》 CAS 2026年第1期25-39,共15页
Background:As a heterogeneous disease,breast cancer requires refined classification frameworks that can effectively guide targeted therapies.However,traditional methods fail to capture the comprehensive molecular insi... Background:As a heterogeneous disease,breast cancer requires refined classification frameworks that can effectively guide targeted therapies.However,traditional methods fail to capture the comprehensive molecular insights needed for this purpose.Methods:To comprehensively capture breast cancer heterogeneity,we employed integrative clustering that incorporates six molecular features from 670 breast cancer samples.Ten distinct clustering algorithms were combined to ensure robust subtype identification,and the identified subtypes were validated in four independent datasets.Subsequently,we constructed a survival support vector machine prognostic model based on key molecular features to enhance survival prediction and clinical applicability.Results:Five novel subtypes were identified:consensus subtypes 1–5(CS1–CS5).CS2 was an aggressive subtype with elevated TP53 mutation rates,high tumor mutational burden,and strong sensitivity to YM-155 and ispinesib.Conversely,CS5 exhibited stable genomics with enhanced nucleotide excision repair and favorable prognoses.CS2 and CS4 showed enriched immune checkpoint expression,indicating potential immunotherapy responsiveness,while CS1 and CS5 exhibited immune-cold profiles.The survival support vector machine model effectively predicted survival outcomes across independent datasets.Conclusions:The refined breast cancer classification framework developed in this research uncovers new insights into molecular heterogeneity,enhances risk stratification,and enables the identification of promising therapeutic targets.The potential of this framework to optimize personalized treatment strategies warrants further clinical validation. 展开更多
关键词 Breast cancer Multi-omics Subtype Prognosis Machine learning
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Pou4f3 Deficiency Obstructs the Subtype Differentiation of Vestibular Hair Cells 认领 引用
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作者 Qin Zhou Yikang Huang +6 位作者 Wenli Ni Mingchuan Feng Lingjie Wu Chuijin Lai Yanping Zhang Wenyan Li Yan Chen 《Neuroscience Bulletin》 SCIE CAS CSCD 2026年第2期349-368,共20页
Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,w... Vestibular hair cells(HCs)in the inner ear,crucial for balance and spatial orientation,are classified into type I and type II subtypes,but the mechanisms regulating their differentiation remain unclear.In this study,we examined the role of Pou4f3,an important transcription factor,in vestibular HC differentiation using Pou4f3DTR/DTR(deficient)and Pou4f3CreER/CreER(knockout)mouse models.In Pou4f3-deficient mice,the HC number decreased,and immature HCs failed to develop type I characteristics,indicating a developmental arrest.While type II HCs differentiated normally,Pou4f3 deficiency disrupted HC bundle formation and cell polarity.Findings from knockout models further confirmed the essential role of Pou4f3 in vestibular HC subtype specification.This study underscores the critical role of Pou4f3 in determining vestibular HC subtypes and offers insights into potential strategies for restoring vestibular function through HC regeneration. 展开更多
关键词 Inner ear Development Vestibular system Auditory system Pou4f3 Hair cell Cell subtype Cell differentiation
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High pathogenicity of Cryptosporidium parvum Ⅱd subtypes in dairy calves 认领 引用
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作者 Xi He Xiaowen Huang +6 位作者 Sheng Guo Weijiang Wang Chaowei Luo Na Li Yaoyu Feng Lihua Xiao Rui Xu 《Animal Diseases》 CAS CSCD 2026年第1期96-103,共8页
Zoonotic cryptosporidiosis is caused primarily by Cryptosporidium parvum.Within C.parvum,theⅡa andⅡd zoonotic subtype families are the most prevalent.TheⅡd subtype family has emerged in China in recent years,causin... Zoonotic cryptosporidiosis is caused primarily by Cryptosporidium parvum.Within C.parvum,theⅡa andⅡd zoonotic subtype families are the most prevalent.TheⅡd subtype family has emerged in China in recent years,causing outbreaks of cryptosporidiosis in dairy calves.The majority of infection studies have been conducted withⅡa subtypes,while the pathogenicity ofⅡd subtypes remains poorly understood.In this study,twoⅡd isolates(ⅡdA20G1-HLJ andⅡdA20G1-HB)from dairy farms in China were used to infect neonatal dairy calves,with aⅡa isolate(ⅡaA17G2R1-Waterborne)from the USA employed as a control.The present study investigated the clinical,parasitological,and pathological characteristics of infected calves.The results demonstrated significantly greater intensity and dura-tion of oocyst shedding inⅡd-infected calves than in control calves.In addition,theⅡdA20G1-HLJ isolate induced peak oocyst shedding of 4.3×107oocysts per gram of feces(OPG)in calves,with oocyst shedding over 106 OPGs at 5-9 d post-infection.In contrast,theⅡaA17G2R1-Waterbrone isolate induced a lower peak oocyst shedding with 8.7×106OPGs,and oocyst shedding with over 106 OPGs occurred at 2-4 d post-infection.Furthermore,calves infected with the twoⅡd isolates presented more severe clinical signs and 20-25%mortality.Calves recovered from the primary infection with theⅡa orⅡd subtype were resistant to a secondary challenge with the heterologous subtype,suggesting the existence of cross-protection between theⅡa andⅡd subtypes.The present data dem-onstrate the high pathogenicity of C.parvumⅡd subtypes in China and the potential crossprotective immunity between theⅡa andⅡd subtypes in calves. 展开更多
关键词 Cryptosporidium Cryptosporidiosis Subtype Calves Pathogenicity
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Transcriptomic Study of Diffuse Large B-Cell Lymphoma Associated with HIV Infection:Identification of Novel Molecular Subtypes 认领 引用
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作者 Yasmine Labiad Céline Baier +4 位作者 Michèle Genin Caroline Besson Sophie Prevot Hubert Lepidi Régis Costello 《Oncology Research》 SCIE 2026年第8期274-288,共15页
Objectives:Transcriptomic profiling has enabled the classification of Diffuse Large B-Cell Lymphoma(DLBCL)into distinct subtypes,such as Germinal Center B-cell-like(GCB)and Activated B-cell-like(ABC),primarily in HIV-... Objectives:Transcriptomic profiling has enabled the classification of Diffuse Large B-Cell Lymphoma(DLBCL)into distinct subtypes,such as Germinal Center B-cell-like(GCB)and Activated B-cell-like(ABC),primarily in HIV-negative patients.However,HIV-associated DLBCL may follow different molecular mechanisms due to immune dysregulation.This study aimed to characterize the transcriptomic landscape of HIV-related DLBCL to identify distinct subtypes and deregulated pathways with potential theranostic implications.Methods:Twelve formalin-fixed,paraffin-embedded DLBCL samples from HIV-positive patients were analyzed using Agilent’s microarray.Quantile normalization and unsupervised hierarchical clustering were performed to classify tumors based on gene expression profiles.Results:Two distinct transcriptomic subgroups were identified.TP53 and BCL7A were overexpressed in cluster I,while BCL2 was overexpressed in cluster II.Notably,the“immune system development”pathway was under expressed in cluster I compared to cluster II.Conclusions:Our findings reveal two molecularly distinct subtypes of HIV-associated DLBCL,likely driven by differences in tumor microenvironment and immune status.These transcriptomic profiles may guide future targeted therapies.Further validation in larger cohorts and integration with proteomic and clinical data are warranted to develop a comprehensive theranostic framework. 展开更多
关键词 Diffuse large B-cell lymphoma HIV-associated lymphoma transcriptomic profiling molecular subtypes gene expression analysis biomarker discovery
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TAP1 Expression Identifies a“Hot-but-exhausted”Glioma Subtype with Distinct Immunobiology and Targetable Dependencies 认领 引用
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作者 Jianlei An Hongru Liu +1 位作者 Jun Zhang Lei Liu 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2026年第7期847-854,共8页
Gliomas are the most common primary brain tumors in adults[1,2].They are highly aggressive,with a poor prognosis.Under the standard treatment regimen of surgery,radiotherapy,and temozolomide,the median overall surv... Gliomas are the most common primary brain tumors in adults[1,2].They are highly aggressive,with a poor prognosis.Under the standard treatment regimen of surgery,radiotherapy,and temozolomide,the median overall survival is only 14–15 months,and the 2-year survival rate is approximately 20%[3].The immunosuppressive microenvironment of gliomas is characterized by abundant regulatory T cells and inhibitory factors such as tumor growth factor beta(TGF-β). 展开更多
关键词 tap expression brain tumors immunobiology regulatory t cells immunosuppressive microenvironment gliomas inhibitory factors hot exhausted glioma subtype
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Metabolic feature-based clustering for subtype identification and longitudinal outcome predictions in the Chinese prediabetic population 认领 引用
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作者 Shu-Han Zhang Jin-Ping Zhang +8 位作者 Lu-Lu Song Li-Li Wu Zhao-Qin Li Yi-Fan He Rui-Fen Deng Wan-Lu Ma Cong Zhang Bo Zhang Li-Ping Yu 《World Journal of Diabetes》 SCIE 2026年第7期162-179,共18页
BACKGROUND In China,the prevalence of prediabetes is alarmingly high,affecting approximately 35.7%of adults.Although lifestyle interventions can reduce diabetes onset,the manifestations of prediabetes vary across indi... BACKGROUND In China,the prevalence of prediabetes is alarmingly high,affecting approximately 35.7%of adults.Although lifestyle interventions can reduce diabetes onset,the manifestations of prediabetes vary across individuals with age,body composition,insulin resistance,and beta-cell function.Therefore,current diagnostic approaches based solely on glucose thresholds are not sufficient,necessitating improved risk stratification through data-driven,unsupervised clustering methods.AIM To investigate the metabolic heterogeneity of prediabetes in Chinese individuals and its association with lifestyle intervention outcomes.METHODS A prospective,multicenter cohort study was conducted in China with 2527 adults aged 18-70 years,at high risk for diabetes.Centers were assigned to either enhanced lifestyle management or standard health education.Enhanced management included individualized dietary energy prescriptions,wearable activity trackers,a mobile co-management app,and structured follow-up.Unsupervised K-means clustering identified four metabolic subtypes.Longitudinal outcomes,including incident diabetes and reversion to normoglycemia,were analyzed using Cox models adjusted for intervention and demographic covariates.RESULTS Four distinct prediabetes subtypes were identified:Mild obesity-related dysmetabolism(MOD,n=177),mild agerelated dysmetabolism(MARD,n=190),severe insulin resistance(n=95),and severe insulin deficiency(n=159).Of 621 participants,367(59.1%)contributed longitudinal data;although attrition differed significantly across subtypes(P<0.001),inverse probability of censoring weighting confirmed the robustness of all estimates.After a median follow-up of 735 days,MOD had a lower risk of diabetes progression than MARD[adjusted hazard ratio(aHR)=0.52,P=0.028]and a greater likelihood of reversion to normoglycemia(aHR=2.08,P=0.049).Adjusted for subtype and sex,enhanced lifestyle management reduced diabetes progression risk(aHR=0.52,95%confidence interval:0.30-0.89;P=0.017),but not reversion to normoglycemia(P=0.159).CONCLUSION Data-driven prediabetes subtyping improved risk stratification.The MOD subtype showed more favorable metabolic trajectories than the MARD subtype.Enhanced lifestyle management was associated with reduced diabetes progression risk. 展开更多
关键词 Prediabetes Metabolic subtypes Longitudinal outcomes Lifestyle intervention Risk stratification
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Overexpression of TFF3 is Associated with Immune Infiltration,Molecular Subtypes,and Clinical Progression in Breast Cancer 认领 引用 被引量：2
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作者 Bei Liu Qin Wang +7 位作者 Rong-fu Huang Xiao-hong Min Han-han Liu Huan Wu Hui Xu Jun-bo Hu Yong-qing Tong Zi-ming Huang 《Current Medical Science》 SCIE CAS CSCD 2026年第2期441-458,共18页
Objective Trefoil factor 3(TFF3),a secreted protein involved in mucosal protection and tumor progression,has an incompletely defined role in breast cancer(BRCA).This study aimed to comprehensively evaluate TFF3 expres... Objective Trefoil factor 3(TFF3),a secreted protein involved in mucosal protection and tumor progression,has an incompletely defined role in breast cancer(BRCA).This study aimed to comprehensively evaluate TFF3 expression patterns,clinical relevance,and prognostic significance in BRCA.Methods Data from the TCGA,GTEx,TNMplot,and TISCH2 databases were integrated to analyze TFF3 expression and clinical significance.Protein expression in clinical samples was validated via immunohistochemistry(IHC),and survival analysis,immune infiltration assessment,and functional enrichment analyses were performed to explore the biological role of TFF3.Results TFF3 was significantly upregulated in BRCA tumor tissues compared with normal tissues(P<0.001)and was expressed predominantly in malignant cells and tumor-associated macrophages.High TFF3 expression correlated strongly with hormone receptor(estrogen receptor/progesterone receptor)positivity,luminal A/B subtypes,and early-stage disease(P<0.01)and showed excellent diagnostic performance for distinguishing basal-like from non-basal-like BRCA(AUC=0.95).TFF3 was an independent protective factor:high expression was associated with improved overall survival(HR=0.75,P=0.02)and disease-free survival(P<0.001),especially in patients receiving hormone therapy(HR=0.89,P=0.0002)or chemotherapy(HR=0.89,P=0.0002).TFF3 exhibited immunomodulatory properties,correlated positively with M2 macrophages and negatively with cytotoxic immune cells(CD8+T cells,NK cells)and checkpoint molecules(PD-1,CTLA-4)(P<0.01).Functional analyses linked TFF3 to estrogen response pathways and cell cycle regulation.IHC validation confirmed TFF3 overexpression in 78.1%of tumors versus 23.9%of normal tissues(P<0.001),with the lowest expression in the basal-like subtype(8.33%vs.59.2%,P=0.0007).Conclusions TFF3 is a robust diagnostic biomarker for BRCA molecular subtyping,an independent prognostic factor,and a potential immunomodulator.These findings highlight its clinical utility for patient stratification and potential as a therapeutic target,particularly in hormone receptor-positive BRCA. 展开更多
关键词 TFF3 Breast cancer Immune microenvironment Prognostic biomarker Molecular subtyping
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Refined immune-based molecular subtypes of gastric cancer:Integrating mismatch repair status and tumor microenvironment for enhanced immunotherapy prediction 认领 引用
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作者 Ke Shen Yanqiang Zhang +12 位作者 Zhiqin Wang Ruixing Xu Jintao He Mengya Zhou Yiming Lu Danni Zhu Yizhou Wei Weiwei Zhu Qing Yang Zhiyuan Xu Can Hu Siwei Pan Xiangdong Cheng 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2026年第2期234-251,共18页
Objective:Gastric cancer(GC)is heterogeneous,and current mismatch repair(MMR)-based classifications incompletely predict response to immune checkpoint inhibitors(ICIs).Methods:RNA sequencing(RNA-seq)and immune infiltr... Objective:Gastric cancer(GC)is heterogeneous,and current mismatch repair(MMR)-based classifications incompletely predict response to immune checkpoint inhibitors(ICIs).Methods:RNA sequencing(RNA-seq)and immune infiltration profiles from 189 resected GC were used to derive four refined immune-MMR subtypes(R1-R4)by integrating MMR status,survival,and tumor microenvironment(TME)features.Multi-omics profiling and pathway analysis defined subtype biology.External transcriptomic cohorts and an ICI-treated cohort were classified with Nearest Template Prediction(NTP).Immune response-associated genes were identified from responder vs.non-responder comparisons within the ICIsensitive subtype and validated by multiplex immunohistochemistry(mIHC).Results:R1 showed the best prognosis and highest immunotherapy response with objective response rate(ORR)54.5%,while R4 had the worst prognosis.R2 represented an immune-unresponsive deficient mismatch repair(dMMR)subset,and R3 captured an immune-active proficient mismatch repair(pMMR)subgroup with moderate therapy sensitivity.Multi-omics integration revealed subtype-specific pathways(e.g.,ECM remodeling in R1,metabolic reprogramming in R2).Reclassification of pMMR tumors based on transcriptional similarity to R1 identified a New R3 subset with enhanced immune features and higher ICI response.Eight immune responseassociated genes(e.g.,CXCL10,CXCL11,ELN,GAD1,IL32,MT1E,OR2I1P,SLC3A1)were identified and validated by mIHC for predictive relevance.Conclusions:This immune-based molecular framework refines risk stratification beyond conventional MMR categories,identifies ICI-sensitive subsets among both dMMR and pMMR tumors,and proposes candidate biomarkers for patient selection. 展开更多
关键词 Mismatch repair deficiency immunologic subtyping tumor microenvironment immunotherapy multi-omics biomarker
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Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm 认领 引用
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作者 Xiao-jie Li Le Chang +8 位作者 Yang Mi Ge Zhang Shan-shan Zhu Yue-xiao Zhang Hao-yu Wang Yi-shuang Lu Ye-xuan Ping Peng-yuan Zheng Xia Xue 《Journal of Integrative Medicine》 SCIE CAS CSCD 2025年第4期445-456,共12页
Objective:Circadian rhythm disruption(CRD)is a risk factor that correlates with poor prognosis across multiple tumor types,including hepatocellular carcinoma(HCC).However,its mechanism remains unclear.This study aimed... Objective:Circadian rhythm disruption(CRD)is a risk factor that correlates with poor prognosis across multiple tumor types,including hepatocellular carcinoma(HCC).However,its mechanism remains unclear.This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity.Methods:To quantify CRD,the HCC CRD score(HCCcrds)was developed.Using machine learning algorithms,we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort(n=369),and the robustness of this method was validated.Furthermore,we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes.Results:We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis.The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis,higher pathological grade,and advanced clinical stages,while the CRD-related subtype with low HCCcrds had better clinical outcomes.We also identified novel biomarkers for each subtype,such as nicotinamide nmethyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1.Conclusion:We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers.Within these groups greater HCCcrds was associated with worse prognosis.This approach has the potential to improve prediction of an individual’s prognosis,guide precision treatments,and assist clinical decision making for HCC patients. 展开更多
关键词 Circadian rhythm disruption Omics Hepatocellular carcinoma subtypes Personalized treatment Precise medicine
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Identification ofMolecular Subtypes and Prognostic Features for Triple-Negative Breast Cancer Based on Golgi Apparatus-Related Gene Signature 认领 引用 被引量：1
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作者 Zhun Yu Jie Wang Guoping Xu 《Oncology Research》 SCIE 2025年第8期2013-2035,共23页
Objectives:Triple-negative breast cancer(TNBC)presents a major treatment challenge due to its aggressive behavior.The dysfunction of the Golgi apparatus(GA)contributes to the development of various cancers.This study ... Objectives:Triple-negative breast cancer(TNBC)presents a major treatment challenge due to its aggressive behavior.The dysfunction of the Golgi apparatus(GA)contributes to the development of various cancers.This study aimed to utilize GA-related genes(GARGs)to forecast the prognosis and immune profile of TNBC.Methods:The data were downloaded from The Cancer Genome Atlas(TCGA)database,including 175 TNBC and 99 healthy samples.The differentially expressed GARGs(DEGARGs)were analyzed using the TCGA biolinks package.The patients with TNBC were classified into two clusters utilizing the ConsensusClusterPlus package according to prognosis-related DEGARGs,followed by comparing the differences in prognosis and immune infiltration between the two clusters.Next,LASSO and stepwise Cox regression were applied to establish a GARGs signature to forecast the TNBC prognosis.The association of the GARGs signature with immune infiltrates and drug sensitivity was further explored.Results:In total,430 DEGARGs were identified between TNBC and healthy samples,among which 20 were related to TNBC prognosis.Two GARG-related molecular clusters associated with different survival times and immune heterogeneity were identified.A risk model for TNBC was established based on six GARGs,and the high-risk(HR)group exhibited a poor prognosis.The HR group demonstrated a distinctly high M2 macrophage infiltration and low M1 macrophage infiltration,which contributed to an immunosuppressive tumor microenvironment and thus led to poor prognosis of the HR group.Immune dysfunction scores and programmed cell death ligand 1(PD-L1)expression were substantially elevated in the HR group.The HR group showed increased sensitivity to anticancer drugs,such as cisplatin.Conclusion:Our findings suggest that GARGs are involved in the pathogenesis of TNBC and provide new insights into prognostic prediction.The identified clusters and GARGs signatures have the potential to guide individualized therapy. 展开更多
关键词 Triple-negative breast cancer(TNBC) Golgi apparatus(GA) prognostic model molecular subtypes drug sensitivity
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Addressing Class Overlap in Sonic Hedgehog Medulloblastoma Molecular Subtypes Classification Using Under-Sampling and SVD-Enhanced Multinomial Regression 认领 引用
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作者 Isra Mohammed Mohamed Elhafiz M.Musa +4 位作者 Murtada K.Elbashir Ayman Mohamed Mostafa Amin Ibrahim Adam Mahmood A.Mahmood Areeg S.Faggad 《Computers, Materials & Continua》 SCIE EI 2025年第8期3749-3763,共15页
Sonic Hedgehog Medulloblastoma(SHH-MB)is one of the four primary molecular subgroups of Medulloblastoma.It is estimated to be responsible for nearly one-third of allMB cases.Using transcriptomic and DNA methylation pr... Sonic Hedgehog Medulloblastoma(SHH-MB)is one of the four primary molecular subgroups of Medulloblastoma.It is estimated to be responsible for nearly one-third of allMB cases.Using transcriptomic and DNA methylation profiling techniques,new developments in this field determined four molecular subtypes for SHH-MB.SHH-MB subtypes show distinct DNAmethylation patterns that allow their discrimination fromoverlapping subtypes and predict clinical outcomes.Class overlapping occurs when two or more classes share common features,making it difficult to distinguish them as separate.Using the DNA methylation dataset,a novel classification technique is presented to address the issue of overlapping SHH-MBsubtypes.Penalizedmultinomial regression(PMR),Tomek links(TL),and singular value decomposition(SVD)were all smoothly integrated into a single framework.SVD and group lasso improve computational efficiency,address the problem of high-dimensional datasets,and clarify class distinctions by removing redundant or irrelevant features that might lead to class overlap.As a method to eliminate the issues of decision boundary overlap and class imbalance in the classification task,TL enhances dataset balance and increases the clarity of decision boundaries through the elimination of overlapping samples.Using fivefold cross-validation,our proposed method(TL-SVDPMR)achieved a remarkable overall accuracy of almost 95%in the classification of SHH-MB molecular subtypes.The results demonstrate the strong performance of the proposed classification model among the various SHH-MB subtypes given a high average of the area under the curve(AUC)values.Additionally,the statistical significance test indicates that TL-SVDPMR is more accurate than both SVM and random forest algorithms in classifying the overlapping SHH-MB subtypes,highlighting its importance for precision medicine applications.Our findings emphasized the success of combining SVD,TL,and PMRtechniques to improve the classification performance for biomedical applications with many features and overlapping subtypes. 展开更多
关键词 Class overlap SHH-MB molecular subtypes under-sampling singular value decomposition penalized multinomial regression DNA methylation profiles
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Single-cell transcriptomic profiling reveals ZEB1-mediated regulation in microglial subtypes and the impact of exercise on neuroinflammatory responses 认领 引用
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作者 Jin-Fang Wu Yi-Sheng Chen Yu-Chun Xie 《Traditional Medicine Research》 2025年第2期55-64,共10页
Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditio... Background:This study aims to identify distinct cellular subtypes within brain tissue using single-cell transcriptomic analysis,focusing on specific biomarkers that differentiate cell types and the effects of traditional and exercise therapy.Methods:Four samples were analyzed:older control(OC),older exercise(OE),younger control(YC),and younger exercise(YE).Single-cell RNA sequencing was used to distinguish cellular subtypes through their biomarker profiles.Data visualization included violin and t-SNE plots to illustrate biomarker expression across cell clusters such as oligodendrocytes,microglia,and astrocytes.Additionally,BV2 cells were exposed to amyloid-beta fragments to simulate Alzheimer’s disease,assessing the impact of exercise-induced cellular responses.Results:Distinct cellular subtypes were identified:oligodendrocytes(MBP,St18),microglia(Dock8),and astrocytes(Aqp4,Gpc5).Sample OE was predominantly oligodendrocytes,while YE had more astrocytes,inhibitory neurons,and Canal-Retzius cells.YC showed a significant presence of Olfm3+ganglion neurons.ZEB1 gene knockout revealed changes in SMAD family gene expression,which regulate ferroptosis.Oxidative stress levels were also evaluated.Conclusion:This profiling enhances our understanding of brain cellular functions and interactions,potentially informing targeted therapies in neurological research.Exercise may influence brain cell immune responses and cell death pathways by regulating specific gene expressions,offering new insights for treating neuroinflammation and degeneration. 展开更多
关键词 single-cell transcriptomics brain tissue cellular subtypes biomarker expression neuronal diversity
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Intrinsic subtypes and bladder cancer metastasis 认领 引用 被引量：5
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作者 David J.McConkey Woonyoung Choi +1 位作者 Andrea Ochoa Colin P.N.Dinney 《Asian Journal of Urology》 2016年第4期260-267,共8页
Recent studies demonstrated that bladder cancers can be grouped into basal and luminal molecular subtypes that possess distinct biological and clinical characteristics.Basal bladder cancers express biomarkers characte... Recent studies demonstrated that bladder cancers can be grouped into basal and luminal molecular subtypes that possess distinct biological and clinical characteristics.Basal bladder cancers express biomarkers characteristic of cancer stem cells and epithelial-tomesenchymal transition(EMT).Patients with basal cancers tend have more advanced stage and metastatic disease at presentation.In preclinical models basal human orthotopic xenografts are also more metastatic than luminal xenografts are,and they metastasize via an EMT-dependent mechanism.However,preclinical and clinical data suggest that basal cancers are also more sensitive to neoadjuvant chemotherapy(NAC),such that most patients with basal cancers who are aggressively managed with NAC have excellent outcomes.Importantly,luminal bladder cancers can also progress to become invasive and metastatic,but they appear to do so via mechanisms that are much less dependent on EMT and may involve help from stromal cells,particularly cancer-associated fibroblasts(CAFs).Although patients with luminal cancers do not appear to derive much clinical benefit from NAC,the luminal tumors that are infiltrated with stromal cells appear to be sensitive to anti-PDL1 antibodies and possibly other immune checkpoint inhibitors.Therefore,neoadjuvant and/or adjuvant immunotherapy may be the most effective approach in treating patients with advanced or metastatic infiltrated luminal bladder cancers. 展开更多
关键词 Bladder cancer Metastasis Basal subtypes Luminal subtypes Epithelial-tomesenchymal transition
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Risk Factors, Clinical Features and Prognosis for Subtypes of Ischemic Stroke in a Chinese Population 认领 引用 被引量：24
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作者 Ya-fu TAN Li-xuan ZHAN +3 位作者 Xiao-hui CHEN Jian-jun QUO Chao QIN En XU 《Current Medical Science》 SCIE CAS 2018年第2期296-303,共8页
It is unanimously accepted that stroke is a highly heterogeneous disorder. Different subtypes of ischemic stroke may have different risk factors, clinical features, and prognoses. The aim of this study was to evaluate... It is unanimously accepted that stroke is a highly heterogeneous disorder. Different subtypes of ischemic stroke may have different risk factors, clinical features, and prognoses. The aim of this study was to evaluate the risk factors, clinical characteristics, and prognoses of different subtypes of ischemic stroke defined by the Trial of ORG10172 in Acute Stroke Treatment （TOAST） criteria. We prospectively analyzed the data from 530 consecutive patients who were admitted to our hospital with acute ischemic stroke within 7 days of stroke onset during the study period. Standardized data assessment was used and the cause of ischemic stroke was classified according to the TOAST criteria. Patients were followed up till 30 and 90 days after stroke onset. It was found that large-artery atherosclerosis was the most frequent etiology of stroke （37.4%）, and showed the highest male preponderance, the highest prevalence of previous transient ischemic attack, and the longest hospital stay among all subtypes. Small artery disease （36.4%） was associated with higher body mass index, higher plasma triglycerides, and lower plasma high-density lipoprotein cholesterol than cardioembolism. Cardioembolism （7.7%）, which was particularly common in the elderly （i.e., individuals aged 65 years and older）, showed the highest female preponderance, the highest prevalence of atrial fibrillation, the earliest presentation to hospital after stroke onset, the most severe symptoms on admission, the maximum complications associated with an adverse outcome, and the highest rate of stroke recurrence and mortality. Our results suggest that ischemic stroke should be regarded as a highly heterogeneous disorder. Studies involving risk factors, clinical features, and prognoses of ischemic stroke should differentiate between etiologic stroke subtypes. 展开更多
关键词 ischemic stroke stroke classification stroke subtypes risk factors clinical features outcome
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Relationship between somatostatin receptor subtype expression and clinicopathology,Ki-67,Bcl-2 and p53 in colorectal cancer 认领 引用 被引量：14
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作者 Cheng-Zhi Qiu Chuan Wang +3 位作者 Zhong-Xin Huang Shi-Ze Zhu You-Yi Wu Jian-Long Qiu 《World Journal of Gastroenterology》 SCIE CAS 2006年第13期2011-2015,共5页
AIM： To study the SSTR1, 2, 3, 4, 5 expression and their relationships with clinico-pathological factors, cell proliferation, Bcl-2 and p53 expression in colorectal cancer cells. METHODS： Immunohistochemical stainin... AIM： To study the SSTR1, 2, 3, 4, 5 expression and their relationships with clinico-pathological factors, cell proliferation, Bcl-2 and p53 expression in colorectal cancer cells. METHODS： Immunohistochemical staining of five SSTR subtypes, Ki-67, Bcl-2 and p53 was performed by the standard streptavidin-peroxidase （SP） technique for the paraffin sections of 127 colorectal cancers, and expression of five SSTR subtypes in 40 specimens of normal colorectal mucosae was detected with the same method. RESULTS： Positive staining for five SSTR subtypes was observed in colorectal cancer cells and normal colorectal mucosae. SSTR1 was the most predominant subtype in both colorectal cancer and normal colorectal mucosa, and the second was SSTR5 or SSTR2. As compared with normal colorectal mucosa, SSTR4 was more frequently expressed in colorectal cancer cells （2.5% vs 18.9%, P〈 0.05）; the expression of SSTR2, 4, 5 in moderately to well differentiated colorectal adenocarcinoma was significantly higher than that in poorly differentiated ones （P〈 0.05）, the SSTR1 expression in colorectal cancer with positive lymph node metastasis was significantly higher than that with negative lymph node metastasis （72.2% and 54.5%, P〈 0.05）. In addition, in the ulcerative type of colorectal cancer, SSTR2 expression was obviously decreased （P 〈 0.05）; the correlation did not reach a statistical significance between the five SSTR subtypes expression and Dukes＇stages （P〉 0.05）, but the frequency of SSTR1 expression increased with Dukes＇ stage, while SSTR3 and SSTR5 expression decreased with Dukes＇ stage. Moreover, there was no correlation between expression of the five SSTR subtypes and other clinicopathological factors such as age, sex, tumor site, tumor depth, distant metastasis. The proliferative indexes in colorectal cancer cells with negative expression of SSTR2 and SSTR3 were significantly higher than that with positive expression （P〈0.05）. The Bcl-2 expression in colorectal cancer cells with positive expression of SSTR1, 2, 3, 5 was significantly lower than that with negative expression （P〈 0.05）. There was no correlation between five SSTR subtypes and p53 expression. CONCLUSION： The most predominant SSTR subtype is SSTR1, and the second is SSTR2 or SSTR5, Five SSTR subtypes play different roles in the development of colorectal cancer, SSTR2 and SSTR3 can inhibit the proliferation and promote apoptosis of tumor cells. 展开更多
关键词 Somatostatin receptor subtype Cell proliferation Apoptosis, p53, Colorectal cancer Immunohistochemistry
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Proteomic characterization of four subtypes of M2 macrophages derived from human THP-1 cells 认领 引用 被引量：12
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作者 Pengfei LI Chen MA +8 位作者 Jing LI Shanshan YOU Liuyi DANG Jingyu WU Zhifang HAO Jun LI Yuan ZHI Lin CHEN Shisheng SUN 《Journal of Zhejiang University-SCIENCE B》 SCIE CAS CSCD 2022年第5期407-422,共16页
Macrophages are widely distributed immune cells that contribute to tissue homeostasis.Human THP-1 cells have been widely used in various macrophage-associated studies,especially those involving pro-inflammatory M1 and... Macrophages are widely distributed immune cells that contribute to tissue homeostasis.Human THP-1 cells have been widely used in various macrophage-associated studies,especially those involving pro-inflammatory M1 and anti-inflammatory M2 phenotypes.However,the molecular characterization of four M2 subtypes(M2a,M2b,M2c,and M2d)derived from THP-1has not been fully investigated.In this study,we systematically analyzed the protein expression profiles of human THP-1-derived macrophages(M0,M1,M2a,M2b,M2c,and M2d)using quantitative proteomics approaches.The commonly and specially regulated proteins of the four M2 subtypes and their potential biological functions were further investigated.The results showed that M2a and M2b,and M2c and M2d have very similar protein expression profiles.These data could serve as an important resource for studies of macrophages using THP-1 cells,and provide a reference to distinguish different M2 subtypes in macrophage-associated diseases for subsequent clinical research. 展开更多
关键词 Macrophage THP-1 cells M2 subtype Proteomics Biological function
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A Reverse-transcription Recombinase-aided Amplification Assay for the Rapid Detection of the Far-Eastern Subtype of Tick-borne Encephalitis Virus 认领 引用 被引量：8
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作者 WANG Qian Ying LI Fan +6 位作者 SHEN Xin Xin FU Shi Hong HE Ying LEI Wen Wen LIANG Guo Dong WANG Huan Yun MA Xue Jun 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2019年第5期357-362,共6页
Objective Tick-borne encephalitis virus(TBEV) is an emerging pathogen in Europe and North Asia that causes tick-borne encephalitis(TBE). A simple, rapid method for detecting TBEV RNA is needed to control this disease.... Objective Tick-borne encephalitis virus(TBEV) is an emerging pathogen in Europe and North Asia that causes tick-borne encephalitis(TBE). A simple, rapid method for detecting TBEV RNA is needed to control this disease. Methods A reverse-transcription recombinase-aided amplification(RT-RAA) assay was developed. This assay can be completed in one closed tube at 39℃ within 30 minutes. The sensitivity and specificity of RT-RAA were validated using non-infectious synthetic RNA representing a fragment of the NS5 region of the wild-type(WT) TBEV genome and the Senzhang strain. Additionally, 10 batches of tick samples were used to evaluate the performance of the RT-RAA assay. Results The analytical limit of detection of the assay was 20 copies per reaction of the TBEV synthetic transcript and 3 plaque-forming units(pfu) per reaction of TBEV titers. With the specific assay, no signal due to other arboviruses was observed. Of the 10 batches of tick samples obtained from the Changbai Mountains of China, three were TBEV-positive, which was consistent with the results of the quantitative real-time PCR assay. Conclusion A rapid, highly sensitive, specific, and easy-to-use method was developed for the detection of the TBEV Far-Eastern subtype. 展开更多
关键词 Tick‐borne encephalitis virus Subtype Far‐eastern Detection RT‐RAA
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Classification of four distinct osteoarthritis subtypes with a knee joint tissue transcriptome atlas 认领 引用 被引量：10
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作者 Chunhui Yuan Zongyou Pan +13 位作者 Kun Zhao Jun Li Zixuan Sheng Xudong Yao Hua Liu Xiaolei Zhang Yang Yang Dongsheng Yu Yu Zhang Yuzi Xu Zhi-Yong Zhang Tianlong Huang Wanlu Liu Hongwei Ouyang 《Bone Research》 SCIE CAS CSCD 2020年第4期406-415,共10页
The limited molecular classifications and disease signatures of osteoarthritis(OA)impede the development of prediagnosis and targeted therapeutics for OA patients.To classify and understand the subtypes of OA,we colle... The limited molecular classifications and disease signatures of osteoarthritis(OA)impede the development of prediagnosis and targeted therapeutics for OA patients.To classify and understand the subtypes of OA,we collected three types of tissue including cartilage,subchondral bone,and synovium from multiple clinical centers and constructed an extensive transcriptome atlas of OA patients.By applying unsupervised clustering analysis to the cartilage transcriptome,OA patients were classified into four subtypes with distinct molecular signatures:a glycosaminoglycan metabolic disorder subtype(C1),a collagen metabolic disorder subtype(C2),an activated sensory neuron subtype(C3),and an inflammation subtype(C4).Through ligand-receptor crosstalk analysis of the three knee tissue types,we linked molecular functions with the clinical symptoms of different OA subtypes.For example,the Gene Ontology functional term of vasculature development was enriched in the subchondral bone-cartilage crosstalk of C2 and the cartilage-subchondral bone crosstalk of C4,which might lead to severe osteophytes in C2 patients and apparent joint space narrowing in C4 patients.Based on the marker genes of the four OA subtypes identified in this study,we modeled OA subtypes with two independent published RNA-seq datasets through random forest classification.The findings of this work contradicted traditional OA diagnosis by medical imaging and revealed distinct molecular subtypes in knee OA patients,which may allow for precise diagnosis and treatment of OA. 展开更多
关键词 diagnosis subtypes knee
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