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
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
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
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
Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predi...Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predict BCa molecular subtypes.Method:We developed a predictive model for BCa molecular subtypes using machine learning(ML)and pathomics derived from Hematoxylin-Eosin stained pathological slides.A cohort of 353 patients from TCGA was employed,and image features were extracted for analysis.Pathomic signatures were constructed using the LASSO Cox regression algorithm,and a pathomic-clinical nomogram was developed and validated in training and testing cohorts.Results:Seventy distinct image features were identified from 150 pathomic signatures.The model demonstrated robust predictive ability,with AUCs of 0.833 and 0.822 in the training and validation cohorts,respectively.The addition of pathomic score,N stage,and M stage improved the model’s discrimination,achieving AUCs of 0.877 and 0.794 in the training and validation cohorts.Limitations include the lack of an external validation cohort.Conclusion:Our ML-based pathomics model shows promise in predicting BCa molecular subtypes and has the potential to enhance prognosis prediction and inform treatment strategies,marking a significant step towards precision medicine for BCa.展开更多
Investigating correlations between radiomic and genomic profiling in breast cancer(BC)molecular subtypes is crucial for understanding disease mechanisms and providing personalized treatment.We present a well-designed ...Investigating correlations between radiomic and genomic profiling in breast cancer(BC)molecular subtypes is crucial for understanding disease mechanisms and providing personalized treatment.We present a well-designed radiogenomic framework image–gene–gene set(IMAGGS),which detects multi-way associations in BC subtypes by integrating radiomic and genomic features.Our dataset consists of 721 patients,each of whom has 12 ultrasound(US)images captured from different angles and gene mutation data.To better characterize tumor traits,12 multi-angle US images are fused using two distinct strategies.Then,we analyze complex many-to-many associations between phenotypic and genotypic features using a machine learning algorithm,deviating from the prevalent one-to-one relationship pattern observed in previous studies.Key radiomic and genomic features are screened using these associations.In addition,gene set enrichment analysis is performed to investigate the joint effects of gene sets and delve deeper into the biological functions of BC subtypes.We further validate the feasibility of IMAGGS in a glioblastoma multiforme dataset to demonstrate the scalability of IMAGGS across different modalities and diseases.Taken together,IMAGGS provides a comprehensive characterization for diseases by associating imaging,genes,and gene sets,paving the way for biological interpretation of radiomics and development of targeted therapy.展开更多
BACKGROUND Cardioneuroablation(CNA)has shown encouraging results in patients with vasovagal syncope(VVS).However,data on different subtypes was scarce.METHODS This observational study retrospectively enrolled 141 pati...BACKGROUND Cardioneuroablation(CNA)has shown encouraging results in patients with vasovagal syncope(VVS).However,data on different subtypes was scarce.METHODS This observational study retrospectively enrolled 141 patients[mean age:40±18 years,51 males(36.2%)]with the diagnosis of VVS.The characteristics among different types of VVS and the outcomes after CNA were analyzed.RESULTS After a mean follow-up of 4.3±1.5 years,41 patients(29.1%)experienced syncope/pre-syncope events after CNA.Syncope/pre-syncope recurrence significantly differed in each subtype(P=0.04).The cardioinhibitory type of VVS had the lowest recurrence rate after the procedure(n=6,16.7%),followed by mixed(n=26,30.6%)and vasodepressive(n=9,45.0%).Additionally,a significant difference was observed in the analyses of the Kaplan-Meier survival curve(P=0.02).Syncope/pre-syncope burden was significantly reduced after CNA in the vasodepressive type(P<0.01).Vasodepressive types with recurrent syncope/pre-syncope after CNA have a lower baseline deceleration capacity(DC)level than those without(7.4±1.0 ms vs.9.0±1.6 ms,P=0.01).Patients with DC<8.4 ms had an 8.1(HR=8.1,95%CI:2.2-30.0,P=0.02)times risk of syncope/pre-syncope recurrence after CNA compared to patients with DC≥8.4 ms,and this association still existed after adjusting for age and sex(HR=8.1,95%CI:2.2-30.1,P=0.02).CONCLUSIONS Different subtypes exhibit different event-free rates.The vasodepressive type exhibited the lowest event-free rate,but those patients with DC≥8.4 ms might benefit from CNA.展开更多
The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characte...The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.展开更多
Background:Pancreatic cancer is a common malignancy with poor prognosis and limited treatment.Here we aimed to investigate the role of host chromosomal instability(CIN)and tumor microbiome in the prognosis of pancreat...Background:Pancreatic cancer is a common malignancy with poor prognosis and limited treatment.Here we aimed to investigate the role of host chromosomal instability(CIN)and tumor microbiome in the prognosis of pancreatic cancer patients.Methods:One hundred formalin-fixed paraffin-embedded(FFPE)pancreatic cancer samples were collected.DNA extracted from FFPE samples were analyzed by low-coverage whole-genome sequencing(WGS)via a customized bioinformatics workflow named ultrasensitive chromosomal aneuploidy detector.Results:Samples were tested according to the procedure of ultrasensitive chromosomal aneuploidy detector(UCAD).We excluded 2 samples with failed quality control,1 patient lost to follow-up and 6 dead in the perioperative period.The final 91 patients were admitted for the following analyses.Thirteen(14.3%)patients with higher CIN score had worse overall survival(OS)than those with lower CIN score.The top 20 microbes in pancreatic cancer samples included 15 species of bacteria and 5 species of viruses.Patients with high human herpesvirus(HHV)-7 and HHV-5 DNA reads exhibited worse OS.Furthermore,we classified 91 patients into 3 subtypes.Patients with higher CIN score(n=13)had the worst prognosis(median OS 6.9 mon);patients with lower CIN score but with HHV-7/5 DNA load(n=24)had worse prognosis(median OS 10.6 mon);while patients with lower CIN score and HHV-7/5 DNA negative(n=54)had the best prognosis(median OS 21.1 mon).Conclusions:High CIN and HHV-7/5 DNA load were associated with worse survival of pancreatic cancer.The novel molecular subtypes of pancreatic cancer based on CIN and microbiome had prognostic value.展开更多
Objective:Triple-negative breast cancer(TNBC)is a heterogeneous and aggressive cancer.Although our previous study classified primary TNBC into four subtypes,comprehensive longitudinal investigations are lacking.Method...Objective:Triple-negative breast cancer(TNBC)is a heterogeneous and aggressive cancer.Although our previous study classified primary TNBC into four subtypes,comprehensive longitudinal investigations are lacking.Methods:We assembled a large-scale,real-world cohort comprised of 880 TNBC patients[465 early-stage TNBC(eTNBC)and 415 metastatic TNBC(mTNBC)patients]who were treated at Fudan University Shanghai Cancer Center.The longitudinal dynamics of TNBC subtypes during disease progression were elucidated in this patient cohort.Comprehensive analysis was performed to compare primary and metastatic lesions within specific TNBC subtypes.Results:The recurrence and metastasis rates within 3 years after initial diagnosis in the eTNBC cohort were 10.1%(47/465).The median overall survival(OS)in the mTNBC cohort was 27.2 months[95%confidence interval(CI),24.4–30.2 months],which indicated a poor prognosis.The prognostic significance of the original molecular subtypes in both eTNBC and mTNBC patients was confirmed.Consistent molecular subtypes were maintained in 77.5%of the patients throughout disease progression with the mesenchymal-like(MES)subtype demonstrating a tendency for subtype transition and brain metastasis.Additionally,a precision treatment strategy based on the metastatic MES subtype of target lesions resulted in improved progression-free survival in the FUTURE trial.Conclusions:Our longitudinal study comprehensively revealed the clinical characteristics and survival of patients with the original TNBC subtypes and validated the consistency of most molecular subtypes throughout disease progression.However,we emphasize the major importance of repeat pathologic confirmation of the MES subtype.展开更多
Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help ...Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.展开更多
Microglia are immune-competent cells involved in maintaining brain homeostasis through their capacity to prune synapses and continuously survey the brain environment.The activation of microglia is one of the most prom...Microglia are immune-competent cells involved in maintaining brain homeostasis through their capacity to prune synapses and continuously survey the brain environment.The activation of microglia is one of the most prominent characteristics of Alzheimer’s disease(AD),a severe neurodegenerative disease featuring extra-cellular deposits of amyloid-βplaques(Aβplaques)and intracellular neurofibrillary tangles(NFTs)as the result of tau hyperphosphorylation.Whether microglia activation is beneficial or detrimental for brains with AD is still con-troversial.In this article,we review recent studies focus-ing on microglia phenotypes in AD by single-cell omics,to understand the signature genes,functions,and regula-tory factors of each phenotype.A profound understanding of the heterogeneity of microglial phenotypes will sug-gest new avenues for treatments for AD.展开更多
Objective:Circulating tumor DNA(ctDNA)is increasingly being used as a potential prognostic biomarker in cancer patients.We aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients ...Objective:Circulating tumor DNA(ctDNA)is increasingly being used as a potential prognostic biomarker in cancer patients.We aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients throughout the whole treatment cycle.Materials and methods:PubMed,Web of Science,Embase,Cochrane Library,Scopus,and clinical trials.gov databases were searched from January 2016 to May 2022.The following search terms were used:ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma.Only studies written in English were included.The following pre-specified criteria should be met for inclusion:(i)original articles,conference abstracts,etc.;(ii)patients with breast cancer;(iii)ctDNA measurement;and(iv)clinical outcome data such as recurrence-free survival(RFS)and overall survival(OS).The random-effects model was preferred considering the potential het-erogeneity across studies.The main outcomes are ctDNA detection rate and postoperative long-term outcomes(RFS and OS).Results:A total of 24 studies were screened.At every measurement time,the ctDNA detection rate of the HR+subgroup was similar to that of the HR-subgroup(P=0.075;P=0.458;P=0.744;and P=0.578),and the ctDNA detection rate of the HER2+subgroup was similar to that of the HER2-subgroup(P=0.805;P=0.271;P=0.807;and P=0.703).In the HR+subgroup,RFS and OS of ctDNA positive patients were similar to those of ctDNA negative patients(P=0.589 and P=0.110),while RFS and OS of the ctDNA positive group was significantly shorter than those of the ctDNA negative patients in the HR-subgroup(HR=4.03,P<0.001;HR=3.21,P<0.001).According to HER grouping,the results were the same as above.In the triple negative breast cancer(TNBC)subgroup,the RFS and OS of ctDNA-positive patients was significantly shorter than of the ctDNA negative patients before and after surgery.Conclusions:ctDNA was more predictive of recurrence-free survival and overall survival in the HR-subgroup than in the HR+subgroup,and the same result was showed in the HER2-subgroup vs.HER2+subgroup.The prognosis of the TNBC subtype is closely related to ctDNA before and after surgery.展开更多
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
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
Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. ...Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient-tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors.展开更多
AIM: To elucidate the differences in somatic, psycho-logical and biochemical pattern between the subtypes of irritable bowel syndrome (IBS). METHODS: Eighty IBS patients, 30 diarrhoea pre-dominant (D-IBS), 16 constipa...AIM: To elucidate the differences in somatic, psycho-logical and biochemical pattern between the subtypes of irritable bowel syndrome (IBS). METHODS: Eighty IBS patients, 30 diarrhoea pre-dominant (D-IBS), 16 constipation predominant (C-IBS) and 34 alternating IBS (A-IBS) underwent physi-otherapeutic examinations for dysfunctions in body movements and awareness and were compared to an apparently healthy control group (AHC). All groups an-swered questionnaires for gastrointestinal and psycho-logical symptoms. Biochemical variables were analysed in blood. RESULTS: The D-IBS group showed less body aware-ness, less psychological symptoms, a more normal sense of coherence and psychosocial rating as well as higher C-peptide values. C-IBS had a higher degree of body dysfunction and psychological symptoms, as well as the lowest sense of coherence compared to controls and D-IBS. They also demonstrated the most elevated prolactin levels. A-IBS had the lowest degree of body disturbance, deteriorated quality of life and affected bi-ochemical pattern. All subtypes had higher pain scores compared to controls. In addition they all had signifi -cantly increased triglycerides and elevated morning cortisol levels, however, without statistical signifi cance compared with the controls.CONCLUSION: IBS subtypes showed different pro-files in body awareness, somatic and psychological symptoms and in biochemical variables. D-IBS differed compared to the other groups by lowered body aware-ness, less psychological symptoms and a higher sense of coherence and elevated C-peptide values. C-IBS and A-IBS subtypes suffered more from depression and anxiety, associated with a lower quality of life. These differences may be important and will be taken into account in our treatment of these patients.展开更多
Objective： To investigate the associations between the different breast cancer subtypes and survival in Chinese women with operable primary breast cancer. Methods： A total of 1538 Chinese women with operable primary...Objective： To investigate the associations between the different breast cancer subtypes and survival in Chinese women with operable primary breast cancer. Methods： A total of 1538 Chinese women with operable primary breast cancer were analyzed in this study, the median follow-up was 77 months. Estrogen receptor （ER）, progesterone receptor （PR）, and HER2 status were available for these patients. Results： Luminal A （ER＋ and/or PR＋, HER2-） had a favorable disease-free survival （DFS） and overall survival （OS） compared with other subtypes in the entire cohort. Using the luminal A as a reference, among the patients with lymph node positive disease, HER2＋ （ER-, PR-, HER2＋） had the worst DFS （hazard ratio, HR=1.80, 95% CI 1.11 to 2.91, P=0.017） and luminal B （ER＋ and/or PR＋, HER2＋） had the worst OS （HR=2.27, 95% CI 1.50 to 3.45, P0.001）; among the patients with lymph node negative disease, triple-negative （ER-, PR-, HER2-） had the worst DFS （HR=2.21, 95% CI 1.43 to 3.41, P0.001）, whereas no significant difference in DFS between HER2＋ and luminal B or luminal A was observed. Conclusion： As compared with luminal A, luminal B and HER2＋ have the worst survival in patients with lymph node positive disease, but this is not the case in patients with lymph node negative disease; triple-negative subtype has a worse survival in both lymph node positive and lymph node negative patients.展开更多
AIM： To explore the propriety of providing hepatitis B virus （HBV） genotypes F and H with two distinct genotypes. METHODS： Eleven HBV isolates of genotype F （HBV/F） were recovered from patients living in San Fra...AIM： To explore the propriety of providing hepatitis B virus （HBV） genotypes F and H with two distinct genotypes. METHODS： Eleven HBV isolates of genotype F （HBV/F） were recovered from patients living in San Francisco, Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carded out among them along with HBV isolates previously reported. RESULTS： Seven of them clustered with reported HBV/F Isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates, and differed by 〉13.7% from HBV isolates of the other six genotypes （A-E and G）. Based on a marked genomic divergence, falling just short of 〉8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47 HBV/F1 isolates as well as 136 representing the other six genotypes （A-E and G）, two clusters separated by distinct genetic distances emerged.CONCLUSION： Based on these analyses, dassifying HBV/ F isolates into two subtypes （F1 and F2） would be more appropriate than providing them with two distinct genotypes （F and H）.展开更多
Summary： Based on the recently proposed Chinese ischemic stroke subclassification （CISS） system, intracranial branch atheromatous disease （BAD） is divided into large artery atherosclerosis （LAA） and penetrating...Summary： Based on the recently proposed Chinese ischemic stroke subclassification （CISS） system, intracranial branch atheromatous disease （BAD） is divided into large artery atherosclerosis （LAA） and penetrating artery disease （PAD）. In the current retrospective analysis, we compared the general charac- teristics of BAD-LAA with BAD-PAD, BAD-LAA with non-BAD-LAA and BAD-PAD with non-BAD-PAD. The study included a total of 80 cases, including 45 cases of BAD and 35 cases of non-BAD. Subjects were classified using CISS system： BAD-LAA, BAD-PAD, non-BAD-LAA and non-BAD-PAD. In addition to analysis of general characteristics, the correlation between the factors and the two subtypes of BAD was evaluated. The number of cases included in the analysis was： 32 cases of BAD-LAA, 13 cases of BAD-PAD, 21 cases of non-BAD-LAA, and 14 cases of non-BAD-PAD. Dia- betes mellitus affected more non-BAD-LAA patients than BAD-LAA patients （P=0.035）. In comparison with non-BAD-PAD, patients with BAD-PAD were younger （P=-0.040）, had higher initial NIHSS score （P〈0.001） and morbidity of ischemic heart disease （P=0.033）. Within patients with BAD, the PAD sub- type was associated with smoking （OR=0.043; P=0.011）, higher low-density lipoprotein （OR=5.339; P=0.029）, ischemic heart disease （OR=9.383; P=0.047） and diabetes mellitus （OR=12.59;P=-0.020）. It was concluded that large artery atherosclerosis was the primary mechanism of BAD. The general char- acteristics showed no significant differences between the CISS subtypes of LAA and PAD within BAD, as well as between the BAD and non-BAD within LAA subtype. Several differences between PAD sub- types of BAD and non-BAD were revealed.展开更多
文摘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.
基金funded by the Deanship of Graduate Studies and Scientific Research at Jouf University under grant No.(DGSSR-2024-02-01137).
文摘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.
基金supported by Tianjian advanced biomedical laboratory key research and development projectHenan Province Natural Science Foundation(grant number:242300421283)+1 种基金Henan Province Science and Technology Research and Development(grant number:242102311176)Henan Province medical science and technology research project(grant number:SBGJ202403038)。
文摘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.
文摘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.
基金supported by the Guangzhou Municipal Basic Research Program Jointly Funded by City,University,and Enterprise Special Project(2024A03J0907)the Natural Science Foundation of Guangdong Province(2024A1515013201)+1 种基金the National Natural Science Foundation of China(82203720,82203188,82002682,81972731,81773026,81972383)the Science and Technology Project of Zhongshan Municipality(No.2024B1032).
文摘Background:Bladder cancer prognosis remains suboptimal despite advancements in research.Current molecular subtyping methods are resource-intensive,highlighting the need for efficient,cost-effective approaches to predict BCa molecular subtypes.Method:We developed a predictive model for BCa molecular subtypes using machine learning(ML)and pathomics derived from Hematoxylin-Eosin stained pathological slides.A cohort of 353 patients from TCGA was employed,and image features were extracted for analysis.Pathomic signatures were constructed using the LASSO Cox regression algorithm,and a pathomic-clinical nomogram was developed and validated in training and testing cohorts.Results:Seventy distinct image features were identified from 150 pathomic signatures.The model demonstrated robust predictive ability,with AUCs of 0.833 and 0.822 in the training and validation cohorts,respectively.The addition of pathomic score,N stage,and M stage improved the model’s discrimination,achieving AUCs of 0.877 and 0.794 in the training and validation cohorts.Limitations include the lack of an external validation cohort.Conclusion:Our ML-based pathomics model shows promise in predicting BCa molecular subtypes and has the potential to enhance prognosis prediction and inform treatment strategies,marking a significant step towards precision medicine for BCa.
基金supported by the National Natural Science Foundation of China(81830058,82071945,91959207,92159301,and 82302212)the Science and Technology Commission of Shanghai Municipality(22ZR1404800)。
文摘Investigating correlations between radiomic and genomic profiling in breast cancer(BC)molecular subtypes is crucial for understanding disease mechanisms and providing personalized treatment.We present a well-designed radiogenomic framework image–gene–gene set(IMAGGS),which detects multi-way associations in BC subtypes by integrating radiomic and genomic features.Our dataset consists of 721 patients,each of whom has 12 ultrasound(US)images captured from different angles and gene mutation data.To better characterize tumor traits,12 multi-angle US images are fused using two distinct strategies.Then,we analyze complex many-to-many associations between phenotypic and genotypic features using a machine learning algorithm,deviating from the prevalent one-to-one relationship pattern observed in previous studies.Key radiomic and genomic features are screened using these associations.In addition,gene set enrichment analysis is performed to investigate the joint effects of gene sets and delve deeper into the biological functions of BC subtypes.We further validate the feasibility of IMAGGS in a glioblastoma multiforme dataset to demonstrate the scalability of IMAGGS across different modalities and diseases.Taken together,IMAGGS provides a comprehensive characterization for diseases by associating imaging,genes,and gene sets,paving the way for biological interpretation of radiomics and development of targeted therapy.
基金supported by the CAMS Central Public Welfare Scientific Research Institute Basal Research Expenses (No.2021-XCGC09-1&No.2022-I2M-C&T-B-045)the Beijing Municipal Science&Technology Commission (Z191100006619019)the High-level Hospital Clinical Scientific Research Business Fees (No.2022-GSP-QZ-4)
文摘BACKGROUND Cardioneuroablation(CNA)has shown encouraging results in patients with vasovagal syncope(VVS).However,data on different subtypes was scarce.METHODS This observational study retrospectively enrolled 141 patients[mean age:40±18 years,51 males(36.2%)]with the diagnosis of VVS.The characteristics among different types of VVS and the outcomes after CNA were analyzed.RESULTS After a mean follow-up of 4.3±1.5 years,41 patients(29.1%)experienced syncope/pre-syncope events after CNA.Syncope/pre-syncope recurrence significantly differed in each subtype(P=0.04).The cardioinhibitory type of VVS had the lowest recurrence rate after the procedure(n=6,16.7%),followed by mixed(n=26,30.6%)and vasodepressive(n=9,45.0%).Additionally,a significant difference was observed in the analyses of the Kaplan-Meier survival curve(P=0.02).Syncope/pre-syncope burden was significantly reduced after CNA in the vasodepressive type(P<0.01).Vasodepressive types with recurrent syncope/pre-syncope after CNA have a lower baseline deceleration capacity(DC)level than those without(7.4±1.0 ms vs.9.0±1.6 ms,P=0.01).Patients with DC<8.4 ms had an 8.1(HR=8.1,95%CI:2.2-30.0,P=0.02)times risk of syncope/pre-syncope recurrence after CNA compared to patients with DC≥8.4 ms,and this association still existed after adjusting for age and sex(HR=8.1,95%CI:2.2-30.1,P=0.02).CONCLUSIONS Different subtypes exhibit different event-free rates.The vasodepressive type exhibited the lowest event-free rate,but those patients with DC≥8.4 ms might benefit from CNA.
文摘The majority of bladder cancers(BCs)are non-muscle invasive BCs(NMIBCs)and show the morphology of a conventional urothelial carcinoma(UC).Aberrant morphology is rare but can be observed.The classification and characterization of histologic subtypes(HS)in UC in BC have mainly been described in muscle in-vasive bladder cancer(MIBC).However,the currently used classification is ap-plied for invasive urothelial neoplasm and therefore,also valid for a subset of NMIBC.The standard transurethral diagnostic work-up misses the presence of HS in NMIBC in a considerable percentage of patients and the real prevalence is not known.HS in NMIBC are associated with an aggressive phenotype.Conse-quently,clinical guidelines categorize HS of NMIBC as“(very)high-risk”tumors and recommend offering radical cystectomy to these patients.Alternative strategies for bladder preservation can only be offered to highly selected patients and ideally within clinical trials.Novel treatment strategies and biomarkers have been established MIBC and NMIBC but have not been comprehensively invest-igated in the context of HS in NMIBC.Further evaluation prior to implementation into clinical practice is needed.
基金supported by grants from the National Natural Science Foundation of China(82171757)the Zhejiang Provincial Natural Science Foundation of China(LZ22H030004 and LQ20H160048).
文摘Background:Pancreatic cancer is a common malignancy with poor prognosis and limited treatment.Here we aimed to investigate the role of host chromosomal instability(CIN)and tumor microbiome in the prognosis of pancreatic cancer patients.Methods:One hundred formalin-fixed paraffin-embedded(FFPE)pancreatic cancer samples were collected.DNA extracted from FFPE samples were analyzed by low-coverage whole-genome sequencing(WGS)via a customized bioinformatics workflow named ultrasensitive chromosomal aneuploidy detector.Results:Samples were tested according to the procedure of ultrasensitive chromosomal aneuploidy detector(UCAD).We excluded 2 samples with failed quality control,1 patient lost to follow-up and 6 dead in the perioperative period.The final 91 patients were admitted for the following analyses.Thirteen(14.3%)patients with higher CIN score had worse overall survival(OS)than those with lower CIN score.The top 20 microbes in pancreatic cancer samples included 15 species of bacteria and 5 species of viruses.Patients with high human herpesvirus(HHV)-7 and HHV-5 DNA reads exhibited worse OS.Furthermore,we classified 91 patients into 3 subtypes.Patients with higher CIN score(n=13)had the worst prognosis(median OS 6.9 mon);patients with lower CIN score but with HHV-7/5 DNA load(n=24)had worse prognosis(median OS 10.6 mon);while patients with lower CIN score and HHV-7/5 DNA negative(n=54)had the best prognosis(median OS 21.1 mon).Conclusions:High CIN and HHV-7/5 DNA load were associated with worse survival of pancreatic cancer.The novel molecular subtypes of pancreatic cancer based on CIN and microbiome had prognostic value.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant No.82103039)the Program of Shanghai Academic/Technology Research Leader(Grant No.20XD1421100)the Wu Jieping Medical Foundation(Grant No.320.6750.2021-10-64).
文摘Objective:Triple-negative breast cancer(TNBC)is a heterogeneous and aggressive cancer.Although our previous study classified primary TNBC into four subtypes,comprehensive longitudinal investigations are lacking.Methods:We assembled a large-scale,real-world cohort comprised of 880 TNBC patients[465 early-stage TNBC(eTNBC)and 415 metastatic TNBC(mTNBC)patients]who were treated at Fudan University Shanghai Cancer Center.The longitudinal dynamics of TNBC subtypes during disease progression were elucidated in this patient cohort.Comprehensive analysis was performed to compare primary and metastatic lesions within specific TNBC subtypes.Results:The recurrence and metastasis rates within 3 years after initial diagnosis in the eTNBC cohort were 10.1%(47/465).The median overall survival(OS)in the mTNBC cohort was 27.2 months[95%confidence interval(CI),24.4–30.2 months],which indicated a poor prognosis.The prognostic significance of the original molecular subtypes in both eTNBC and mTNBC patients was confirmed.Consistent molecular subtypes were maintained in 77.5%of the patients throughout disease progression with the mesenchymal-like(MES)subtype demonstrating a tendency for subtype transition and brain metastasis.Additionally,a precision treatment strategy based on the metastatic MES subtype of target lesions resulted in improved progression-free survival in the FUTURE trial.Conclusions:Our longitudinal study comprehensively revealed the clinical characteristics and survival of patients with the original TNBC subtypes and validated the consistency of most molecular subtypes throughout disease progression.However,we emphasize the major importance of repeat pathologic confirmation of the MES subtype.
文摘Background:Cytotoxic T lymphocytes(CD8+T)cells function critically in mediating anti-tumor immune response in cancer patients.Characterizing the specific functions of CD8+T cells in lung adenocarcinoma(LUAD)could help better understand local anti-tumor immune responses and estimate the effect of immunotherapy.Methods:Gens related to CD8+T cells were identified by cluster analysis based on the single-cell sequencing data of three LUAD tissues and their paired normal tissues.Weighted gene co-expression network analysis(WGCNA),consensus clustering,differential expression analysis,least absolute shrinkage and selection operator(LASSO)and Cox regression analysis were conducted to classify molecular subtypes for LUAD and to develop a risk model using prognostic genes related to CD8+T cells.Expression of the genes in the prognostic model,their effects on tumor cell invasion,and interactions with CD8+T cells were verified by cell experiments.Results:This study defined two LUAD clusters(CD8+0 and CD8+1)based on CD8+T cells,with cluster CD8+0 being significantly associated with the prognosis of LUAD.Three heterogeneous subtypes(clusters 1,2,and 3)differing in prognosis,genome mutation events,and immune status were categorized using 42 prognostic genes.A prognostic model created based on 11 significant genes(including CD200R1,CLEC17A,ZC3H12D,GNG7,SNX30,CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2,and KRT81)was able to independently estimate the death risk for patients in different LUAD cohorts.Moreover,the model also showed general applicability in external validation cohorts.Low-risk patients could benefit more from taking immunotherapy and were significantly related to the resistance to anticancer drugs.The results from cell experiments demonstrated that the expression of CD200R1,CLEC17A,ZC3H12D,GNG7,and SNX30 was significantly downregulated,while that of CDCP1,NEIL3,IGF2BP1,RHOV,ABCC2 and KRT81 was upregulated in LUAD cells.Inhibition of CD200R1 greatly increased the invasiveness of the LUAD cells,but inhibiting CDCP1 expression weakened the invasion ability of LUAD cells.Conclusion:This study defined two prognostic CD8+T cell clusters and classified three heterogeneous molecular subtypes for LUAD.A prognostic model predictive of the potential effects of immunotherapy on LUAD patients was developed.
文摘Microglia are immune-competent cells involved in maintaining brain homeostasis through their capacity to prune synapses and continuously survey the brain environment.The activation of microglia is one of the most prominent characteristics of Alzheimer’s disease(AD),a severe neurodegenerative disease featuring extra-cellular deposits of amyloid-βplaques(Aβplaques)and intracellular neurofibrillary tangles(NFTs)as the result of tau hyperphosphorylation.Whether microglia activation is beneficial or detrimental for brains with AD is still con-troversial.In this article,we review recent studies focus-ing on microglia phenotypes in AD by single-cell omics,to understand the signature genes,functions,and regula-tory factors of each phenotype.A profound understanding of the heterogeneity of microglial phenotypes will sug-gest new avenues for treatments for AD.
基金funded by the Capital’s Funds for Health Improve-ment and Research(grant number:2024-1G-4023)the Special Project for Director,China Center for Evidence Based Traditional Chinese Medicine(grant number:2020YJSZX-2)the National Natural Sci-ence Foundation of China(grant number:72074011)。
文摘Objective:Circulating tumor DNA(ctDNA)is increasingly being used as a potential prognostic biomarker in cancer patients.We aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients throughout the whole treatment cycle.Materials and methods:PubMed,Web of Science,Embase,Cochrane Library,Scopus,and clinical trials.gov databases were searched from January 2016 to May 2022.The following search terms were used:ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma.Only studies written in English were included.The following pre-specified criteria should be met for inclusion:(i)original articles,conference abstracts,etc.;(ii)patients with breast cancer;(iii)ctDNA measurement;and(iv)clinical outcome data such as recurrence-free survival(RFS)and overall survival(OS).The random-effects model was preferred considering the potential het-erogeneity across studies.The main outcomes are ctDNA detection rate and postoperative long-term outcomes(RFS and OS).Results:A total of 24 studies were screened.At every measurement time,the ctDNA detection rate of the HR+subgroup was similar to that of the HR-subgroup(P=0.075;P=0.458;P=0.744;and P=0.578),and the ctDNA detection rate of the HER2+subgroup was similar to that of the HER2-subgroup(P=0.805;P=0.271;P=0.807;and P=0.703).In the HR+subgroup,RFS and OS of ctDNA positive patients were similar to those of ctDNA negative patients(P=0.589 and P=0.110),while RFS and OS of the ctDNA positive group was significantly shorter than those of the ctDNA negative patients in the HR-subgroup(HR=4.03,P<0.001;HR=3.21,P<0.001).According to HER grouping,the results were the same as above.In the triple negative breast cancer(TNBC)subgroup,the RFS and OS of ctDNA-positive patients was significantly shorter than of the ctDNA negative patients before and after surgery.Conclusions:ctDNA was more predictive of recurrence-free survival and overall survival in the HR-subgroup than in the HR+subgroup,and the same result was showed in the HER2-subgroup vs.HER2+subgroup.The prognosis of the TNBC subtype is closely related to ctDNA before and after surgery.
文摘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.
文摘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.
文摘Breast cancer is a heterogeneous complex of diseases, a spectrum of many subtypes with distinct biological features that lead to differences in response patterns to various treatment modalities and clinical outcomes. Traditional classification systems regarding biological characteristics may have limitations for patient-tailored treatment strategies. Tumors with similar clinical and pathological presentations may have different behaviors. Analyses of breast cancer with new molecular techniques now hold promise for the development of more accurate tests for the prediction of recurrence. Gene signatures have been developed as predictors of response to therapy and protein gene products that have direct roles in driving the biology and clinical behavior of cancer cells are potential targets for the development of novel therapeutics. The present review summarizes current knowledge in breast cancer molecular biology, focusing on novel prognostic and predictive factors.
基金Grants from the University of Gothenburg, Sweden
文摘AIM: To elucidate the differences in somatic, psycho-logical and biochemical pattern between the subtypes of irritable bowel syndrome (IBS). METHODS: Eighty IBS patients, 30 diarrhoea pre-dominant (D-IBS), 16 constipation predominant (C-IBS) and 34 alternating IBS (A-IBS) underwent physi-otherapeutic examinations for dysfunctions in body movements and awareness and were compared to an apparently healthy control group (AHC). All groups an-swered questionnaires for gastrointestinal and psycho-logical symptoms. Biochemical variables were analysed in blood. RESULTS: The D-IBS group showed less body aware-ness, less psychological symptoms, a more normal sense of coherence and psychosocial rating as well as higher C-peptide values. C-IBS had a higher degree of body dysfunction and psychological symptoms, as well as the lowest sense of coherence compared to controls and D-IBS. They also demonstrated the most elevated prolactin levels. A-IBS had the lowest degree of body disturbance, deteriorated quality of life and affected bi-ochemical pattern. All subtypes had higher pain scores compared to controls. In addition they all had signifi -cantly increased triglycerides and elevated morning cortisol levels, however, without statistical signifi cance compared with the controls.CONCLUSION: IBS subtypes showed different pro-files in body awareness, somatic and psychological symptoms and in biochemical variables. D-IBS differed compared to the other groups by lowered body aware-ness, less psychological symptoms and a higher sense of coherence and elevated C-peptide values. C-IBS and A-IBS subtypes suffered more from depression and anxiety, associated with a lower quality of life. These differences may be important and will be taken into account in our treatment of these patients.
基金supported by grants from the Program fro Breast Cancer Tissue Bank of Beijingthe National Natural Science Foundation of China (No.30973436)
文摘Objective： To investigate the associations between the different breast cancer subtypes and survival in Chinese women with operable primary breast cancer. Methods： A total of 1538 Chinese women with operable primary breast cancer were analyzed in this study, the median follow-up was 77 months. Estrogen receptor （ER）, progesterone receptor （PR）, and HER2 status were available for these patients. Results： Luminal A （ER＋ and/or PR＋, HER2-） had a favorable disease-free survival （DFS） and overall survival （OS） compared with other subtypes in the entire cohort. Using the luminal A as a reference, among the patients with lymph node positive disease, HER2＋ （ER-, PR-, HER2＋） had the worst DFS （hazard ratio, HR=1.80, 95% CI 1.11 to 2.91, P=0.017） and luminal B （ER＋ and/or PR＋, HER2＋） had the worst OS （HR=2.27, 95% CI 1.50 to 3.45, P0.001）; among the patients with lymph node negative disease, triple-negative （ER-, PR-, HER2-） had the worst DFS （HR=2.21, 95% CI 1.43 to 3.41, P0.001）, whereas no significant difference in DFS between HER2＋ and luminal B or luminal A was observed. Conclusion： As compared with luminal A, luminal B and HER2＋ have the worst survival in patients with lymph node positive disease, but this is not the case in patients with lymph node negative disease; triple-negative subtype has a worse survival in both lymph node positive and lymph node negative patients.
文摘AIM： To explore the propriety of providing hepatitis B virus （HBV） genotypes F and H with two distinct genotypes. METHODS： Eleven HBV isolates of genotype F （HBV/F） were recovered from patients living in San Francisco, Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carded out among them along with HBV isolates previously reported. RESULTS： Seven of them clustered with reported HBV/F Isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates, and differed by 〉13.7% from HBV isolates of the other six genotypes （A-E and G）. Based on a marked genomic divergence, falling just short of 〉8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47 HBV/F1 isolates as well as 136 representing the other six genotypes （A-E and G）, two clusters separated by distinct genetic distances emerged.CONCLUSION： Based on these analyses, dassifying HBV/ F isolates into two subtypes （F1 and F2） would be more appropriate than providing them with two distinct genotypes （F and H）.
文摘Summary： Based on the recently proposed Chinese ischemic stroke subclassification （CISS） system, intracranial branch atheromatous disease （BAD） is divided into large artery atherosclerosis （LAA） and penetrating artery disease （PAD）. In the current retrospective analysis, we compared the general charac- teristics of BAD-LAA with BAD-PAD, BAD-LAA with non-BAD-LAA and BAD-PAD with non-BAD-PAD. The study included a total of 80 cases, including 45 cases of BAD and 35 cases of non-BAD. Subjects were classified using CISS system： BAD-LAA, BAD-PAD, non-BAD-LAA and non-BAD-PAD. In addition to analysis of general characteristics, the correlation between the factors and the two subtypes of BAD was evaluated. The number of cases included in the analysis was： 32 cases of BAD-LAA, 13 cases of BAD-PAD, 21 cases of non-BAD-LAA, and 14 cases of non-BAD-PAD. Dia- betes mellitus affected more non-BAD-LAA patients than BAD-LAA patients （P=0.035）. In comparison with non-BAD-PAD, patients with BAD-PAD were younger （P=-0.040）, had higher initial NIHSS score （P〈0.001） and morbidity of ischemic heart disease （P=0.033）. Within patients with BAD, the PAD sub- type was associated with smoking （OR=0.043; P=0.011）, higher low-density lipoprotein （OR=5.339; P=0.029）, ischemic heart disease （OR=9.383; P=0.047） and diabetes mellitus （OR=12.59;P=-0.020）. It was concluded that large artery atherosclerosis was the primary mechanism of BAD. The general char- acteristics showed no significant differences between the CISS subtypes of LAA and PAD within BAD, as well as between the BAD and non-BAD within LAA subtype. Several differences between PAD sub- types of BAD and non-BAD were revealed.
