Background: Breast cancer is a genetically and clinically heterogeneous disease with multiple subtypes. The classification of these subtypes has evolved over the years. The most common and widely accepted classificati...Background: Breast cancer is a genetically and clinically heterogeneous disease with multiple subtypes. The classification of these subtypes has evolved over the years. The most common and widely accepted classification of breast cancer is from an immunohistochemical perspective, based on the expression of the following hormone receptors: Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor (HER2). Accordingly, the following four subtypes of breast cancer are widely recognized—Luminal A, Luminal B, HER2 Enriched and Triple Negative. Breast cancer management approaches include surgery, chemotherapy, radiotherapy and targeted hormone therapy necessitated by molecular subtyping. Aims: This study aimed to determine the level of adherence to breast cancer molecular subtyping among women with breast cancer attending tertiary health facilities in Imo State. Methodology: Immunohistochemistry reports of women with breast cancer attending tertiary health facilities in Imo State were retrieved from patient’s case files. Tissue blocks were also retrieved from tissue block archives of both hospitals for women who did not take up immunohistochemistry services after their initial diagnosis and also those whose immunohistochemistry reports were not found in their case files. Results: Among the 121 women that participated in the study, there were in all 74 (61.2%) had molecular subtyping of their tumour blocks. Up to 45 (37.2%) did not go for molecular subtyping of their tumour blocks while 2 (1.7%) were not sure whether they had or not. Conclusion: It, therefore, depicts that the rate of uptake was found as 61.2% among the participants and there is a need to create more awareness of the importance of molecular subtyping, which necessitates the use of targeted hormone therapy.展开更多
Background:Breast cancer is the most common cancer,and abnormal lipid metabolism is associated with cancer.APOD expression is negatively correlated with various cancers related to tumor prognosis.DNA methylation may a...Background:Breast cancer is the most common cancer,and abnormal lipid metabolism is associated with cancer.APOD expression is negatively correlated with various cancers related to tumor prognosis.DNA methylation may affect APOD expression.Therefore,this paper aims to investigate the significance of APOD expression and APOD DNA methylation in breast cancer.Methods:This study utilized comprehensive bioinformatics analysis of APOD using Gene Expression database of Normal and Tumor tissues 2,UCSC Xena,etc.Clinical and survival information obtained from the The Cancer Genome Atlas and Gene Expression Omnibus datasets were extracted for data mining.Results:The correlation between APOD and breast cancer was examined,along with the connection between APOD DNA methylation and APOD expression.In the The Cancer Genome Atlas cohort,as well as GSE31448 and GSE65194 datasets,APOD expression decreased in breast cancer(P<0.0001).Clinical feature analysis results showed that APOD expression was correlated with the PAM50 subtype,with the lowest expression in the Basal subtype(P<0.0001).High APOD expression is a good prognostic marker for breast cancer(HR=0.71,P=0.037).APOD methylation level was significantly negatively correlated with expression level(R=−0.4770,P<0.001),and cg15231202,cg23720929,and cg05624196 were important regulatory targets.High APOD expression was associated with higher metabolism and extracellular matrix scores.Conclusion:APOD is an independent prognostic marker for breast cancer and is regulated by DNA methylation to modulate mRNA expression.展开更多
Listeria monocytogenes,one of the most important foodborne pathogens,can cause listeriosis,a lethal disease for humans.L.ivanovii,which is closely related to L.monocytogenes,is also widely distributed in nature and in...Listeria monocytogenes,one of the most important foodborne pathogens,can cause listeriosis,a lethal disease for humans.L.ivanovii,which is closely related to L.monocytogenes,is also widely distributed in nature and infects mainly warm-blooded ruminants,causing economic loss.Thus,there are high priority needs for methodologies for rapid,specific,cost-effective and accurate detection,characterization and subtyping of L.monocytogenes and L.ivanovii in foods and environmental sources.In this review,we(A)described L.monocytogenes and L.ivanovii,world-wide incidence of listeriosis,and prevalence of various L.monocytogenes strains in food and environmental sources;(B)comprehensively reviewed different types of traditional and newly developed methodologies,including culture-based,antigen/antibody-based,LOOP-mediated isothermal amplification,matrix-assisted laser desorption ionization-time of flight-mass spectrometry,DNA microarray,and genomic sequencing for detection and characterization of L.monocytogenes in foods and environmental sources;(C)comprehensively summarized different subtyping methodologies,including pulsed-field gel electrophoresis,multi-locus sequence typing,ribotyping,and phage-typing,and whole genomic sequencing etc.for subtyping of L.monocytogenes strains from food and environmental sources;and(D)described the applications of these methodologies in detection and subtyping of L.monocytogenes in foods and food processing facilities.展开更多
Objective To analyze the value of multi-slice spiral CT ( SCT) scan in staging and subtyping of renal cell carcinoma ( RCC) . Methods The preoperative kidney SCT data and postoperative pathology results of 64 patients...Objective To analyze the value of multi-slice spiral CT ( SCT) scan in staging and subtyping of renal cell carcinoma ( RCC) . Methods The preoperative kidney SCT data and postoperative pathology results of 64 patients with RCC were retrospectively analyzed. The pa-展开更多
The prevalence of type 2 diabetes mellitus(T2DM)is increasing rapidly worldwide.Because of the limited success of generic interventions,the focus of the disease study has shifted toward personalized strategies,particu...The prevalence of type 2 diabetes mellitus(T2DM)is increasing rapidly worldwide.Because of the limited success of generic interventions,the focus of the disease study has shifted toward personalized strategies,particularly in the early stages of the disease.Traditional Chinese medicine(TCM)is based on a systems view combined with personalized strategies and has improved our knowledge of personalized diagnostics.From a systems biology perspective,the understanding of personalized diagnostics can be improved to yield a biochemical basis for such strategies;for example,metabolomics can be used in combination with other system-based diagnostic methods such as ultra-weak photon emission(UPE).In this study,we investigated the feasibility of using plasma metabolomics obtained from 44 pre-T2DM subjects to stratify the following TCM-based subtypes:Qi-Yin deficiency,Qi-Yin deficiency with dampness,and Qi-Yin deficiency with stagnation.We studied the relationship between plasma metabolomics and UPE with respect to TCM-based subtyping in order to obtain biochemical information for further interpreting disease subtypes.Principal component analysis of plasma metabolites revealed differences among the TCM-based pre-T2DM subtypes.Relatively high levels of lipids(e.g.,cholesterol esters and triglycerides)were important discriminators of two of the three subtypes and may be associated with a higher risk of cardiovascular disease.Plasma metabolomics data indicate that the lipid profile is an essential component captured by UPE with respect to stratifying subtypes of T2DM.The results suggest that metabolic differences exist among different TCM-based subtypes of pre-T2DM,and profiling plasma metabolites can be used to discriminate among these subtypes.Plasma metabolomics thus provides biochemical insights into system-based UPE measurements.展开更多
Objective:To investigate Blastocystis’etiologic role and association with gastrointestinal symptomatology in acute and chronic urticaria patients and to identify Blastocystis subtypes responsible for urticaria.Method...Objective:To investigate Blastocystis’etiologic role and association with gastrointestinal symptomatology in acute and chronic urticaria patients and to identify Blastocystis subtypes responsible for urticaria.Methods:The study included urticaria patients and healthy individuals that presented to our polyclinic between June 2015 and May 2017.The participants were assigned into Group栺(137 patients),subdivided into acute(72)and chronic urticaria patients(65),and Group栻(129 control individuals).Blastocystis presence was investigated by native-Lugol examination,trichrome staining,PCR using sequence tagged site primers,and DNA sequencing analysis.The phylogenetic tree was constructed.Results:The native-Lugol and trichrome staining methods revealed that 16 patients(16/133,12.0%)had Blastocystis-positive stool samples,of which seven samples(7/133,5.3%)belonged acute and nine(9/133,6.8%)to chronic urticaria patients.Concerning Blastocystis subtypes,of the acute urticaria patients,three had subtype 1(ST1),one had ST2,and three had ST3.Of the chronic urticaria patients,one had ST1 and eight had ST3.Blastocystis positivity was detected in two control individuals(2/123,1.6%),both being ST3.All subtypes identified by PCR were confirmed by the sequencing analysis.The acute and chronic urticaria groups showed no statistically significant differences for Blastocystis positivity(P=0.60)and subtype distribution(P=0.15).A statistically significant difference was found between the urticaria patients and the controls for Blastocystis positivity(P<0.01),but not for subtype distribution(P=0.67)or for Blastocystis presence and gastrointestinal complaints.Conclusions:This study on Blastocystis subtype distribution among Turkish urticaria patients showed results consistent with the literature.It was concluded that Blastocystis should be kept in mind in patients with urticaria.展开更多
Hepatocellular carcinoma(HCC)is one of the most prevalent and fatal digestive tumors.Treatment for this disease has been constraint by heterogeneity of this group of tumors,which has greatly limited the progress in pe...Hepatocellular carcinoma(HCC)is one of the most prevalent and fatal digestive tumors.Treatment for this disease has been constraint by heterogeneity of this group of tumors,which has greatly limited the progress in personalized therapy.Although existing studies have revealed the genetic and epigenetic blueprints that drive HCCs,many of the molecular mechanisms that lead to HCCs remain elusive.Recent advances in techniques for studying functional genomics,such as genome sequencing and transcriptomic analyses,have led to the discovery of molecular mechanisms that participate in the initiation and evolution of HCC.Integrative multi-omics analyses have identified several molecular subtypes of HCC associated with specific molecular characteristics and clinical outcomes.Deciphering similar molecular features among highly heterogeneous HCC patients is a prerequisite to implementation of personalized therapeutics.This review summarizes the current research progresses in precision therapy on the backbone of molecular subtypes of HCC.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
BACKGROUND Macrotrabecular-massive hepatocellular carcinoma(MTM-HCC)is closely related to aggressive phenotype,gene mutation,carcinogenic pathway,and immunohistochemical markers and is a strong independent predictor o...BACKGROUND Macrotrabecular-massive hepatocellular carcinoma(MTM-HCC)is closely related to aggressive phenotype,gene mutation,carcinogenic pathway,and immunohistochemical markers and is a strong independent predictor of early recurrence and poor prognosis.With the development of imaging technology,successful applications of contrast-enhanced magnetic resonance imaging(MRI)have been reported in identifying the MTM-HCC subtype.Radiomics,as an objective and beneficial method for tumour evaluation,is used to convert medical images into high-throughput quantification features that greatly push the development of precision medicine.AIM To establish and verify a nomogram for preoperatively identifying MTM-HCC by comparing different machine learning algorithms.METHODS This retrospective study enrolled 232(training set,162;test set,70)hepatocellular carcinoma patients from April 2018 to September 2021.A total of 3111 radiomics features were extracted from dynamic contrast-enhanced MRI,followed by dimension reduction of these features.Logistic regression(LR),K-nearest neighbour(KNN),Bayes,Tree,and support vector machine(SVM)algorithms were used to select the best radiomics signature.We used the relative standard deviation(RSD)and bootstrap methods to quantify the stability of these five algorithms.The algorithm with the lowest RSD represented the best stability,and it was used to construct the best radiomics model.Multivariable logistic analysis was used to select the useful clinical and radiological features,and different predictive models were established.Finally,the predictive performances of the different models were assessed by evaluating the area under the curve(AUC).RESULTS The RSD values based on LR,KNN,Bayes,Tree,and SVM were 3.8%,8.6%,4.3%,17.7%,and 17.4%,respectively.Therefore,the LR machine learning algorithm was selected to construct the best radiomics signature,which performed well with AUCs of 0.766 and 0.739 in the training and test sets,respectively.In the multivariable analysis,age[odds ratio(OR)=0.956,P=0.034],alphafetoprotein(OR=10.066,P<0.001),tumour size(OR=3.316,P=0.002),tumour-to-liver apparent diffusion coefficient(ADC)ratio(OR=0.156,P=0.037),and radiomics score(OR=2.923,P<0.001)were independent predictors of MTM-HCC.Among the different models,the predictive performances of the clinical-radiomics model and radiological-radiomics model were significantly improved compared to those of the clinical model(AUCs:0.888 vs 0.836,P=0.046)and radiological model(AUCs:0.796 vs 0.688,P=0.012),respectively,in the training set,highlighting the improved predictive performance of radiomics.The nomogram performed best,with AUCs of 0.896 and 0.805 in the training and test sets,respectively.CONCLUSION The nomogram containing radiomics,age,alpha-fetoprotein,tumour size,and tumour-to-liver ADC ratio revealed excellent predictive ability in preoperatively identifying the MTM-HCC subtype.展开更多
BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a rare distinct subtype of precursor lesions of biliary carcinoma.IPNB is considered to originate from luminal biliary epithelial cells,typically disp...BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a rare distinct subtype of precursor lesions of biliary carcinoma.IPNB is considered to originate from luminal biliary epithelial cells,typically displays mucin-hypersecretion or a papillary growth pattern,and results in cystic dilatation[1].IPNB develops anywhere in the intrahepatic and extrahepatic biliary tracts,and can occur in various pathological stages from low-grade dysplasia to invasive carcinoma.IPNBs have similar phenotypic changes in the occurrence and development of all subtypes,and the prognosis is significantly better than that of traditional(nonpapillary)cholangiocarcinoma.AIM To evaluate the clinicopathological features of IPNB to provide evidence-based guidance for treatment.METHODS Invasive IPNB,invasive intraductal papillary mucinous neoplasm of the pancreas(IPMN),and traditional cholangiocarcinoma data for affected individuals from 1975 to 2016 were obtained from the Surveillance,Epidemiology,and End Results(SEER)database.Annual percentage changes(APCs)in the incidence and incidence-based(IB)mortality were calculated.We identified the independent predictors of overall survival(OS)and cancer-specific survival(CSS)in indivi duals with invasive IPNB.RESULTS The incidence and IB mortality of invasive IPNB showed sustained decreases,with an APC of-4.5%(95%CI:-5.1%to-3.8%)and-3.3%(95%CI:-4.1%to-2.6%)(P<0.001),respectively.Similar decreases in incidence and IB mortality were seen for invasive IPMN but not for traditional cholangiocarcinoma.Both OS and CSS for invasive IPNB were better than for invasive IPMN and traditional cholangiocarcinoma.A total of 1635 individuals with invasive IPNB were included in our prognosis analysis.The most common tumor sites were the pancreaticobiliary ampulla(47.9%)and perihilar tract(36.7%),but the mucin-related subtype of invasive IPNB was the main type,intrahepatically(approximately 90%).In the univariate and multivariate Cox regression analysis,age,tumor site,grade and stage,subtype,surgery,and chemotherapy were associated with OS and CSS(P<0.05).CONCLUSION Incidence and IB mortality of invasive IPNB trended steadily downward.The heterogeneity of IPNB comprises site and the tumor’s mucin-producing status.展开更多
Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resist...Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise treatment.Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological memory.Multiple conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains unsatisfactory.Compared with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer.This review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.展开更多
Mechanical forces shape the development,function,and survival of every cell within the central nervous system(CNS)but are particularly important for astroglia,a subtype of glial cell that mediates communication betwee...Mechanical forces shape the development,function,and survival of every cell within the central nervous system(CNS)but are particularly important for astroglia,a subtype of glial cell that mediates communication between neurons and blood vessels.展开更多
Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunot...Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunotherapeutic strategy has attracted much attention for various diseases,however,its application in CHOL is limited due to the thoughtlessness in the integration of vaccine design and patient selection.A recent study established an integrated path for identifying potent CHOL antigens for mRNA vaccine development and a precise stratification for identifying CHOL patients who can benefit from the mRNA vaccines.In spite of a promising prospect,further investigations should identify immunogenic antigens and onco-immunological characteristics of CHOL to guide the clinical application of CHOL mRNA vaccines in the future.展开更多
Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted ...Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.展开更多
Pancreatic cancer is associated with high mortality and is one of the most aggressive of malignancies,but studies have not fully evaluated its molecular subtypes,prognosis and response to immunotherapy of different su...Pancreatic cancer is associated with high mortality and is one of the most aggressive of malignancies,but studies have not fully evaluated its molecular subtypes,prognosis and response to immunotherapy of different subtypes.The purpose of this study was to explore the molecular subtypes and the key genes associated with the prognosis of pancreas cancer patients and study the clinical phenotype,prognosis and response to immunotherapy using single-cell seq data and bulk RNA seq data,and data retrieved from GEO and TCGA databases.Methods:Single-cell seq data and bioinformatics methods were used in this study.Pancreatic cancer data were retrieved from GEO and TCGA databases,the molecular subtypes of pancreatic cancer were determined using the six cGAS-STING related pathways,and the clinical phenotype,mutation,immunological characteristics and pathways related to pancreatic cancer were evaluated.Results:Pancreatic cancer was classified into 3 molecular subtypes,and survival analysis revealed that patients in Cluster3(C3)had the worst prognosis,whereas Cluster1(C1)had the best prognosis.The clinical phenotype and gene mutation were statistically different among the three molecular subtypes.Analysis of immunotherapy response revealed that most immune checkpoint genes were differentially expressed in the three subtypes.A lower risk of immune escape was observed in Cluster1(C1),indicating higher sensitivity to immunotherapeutic drugs and subjects in this Cluster are more likely to benefit from immunotherapy.The pathways related to pancreatic cancer were differentially enriched among the three subtypes.Five genes,namely SFRP1,GIPR,EMP1,COL17A and CXCL11 were selected to construct a prognostic signature.Conclusions:Single-cell seq data were to classify pancreatic cancer into three molecular subtypes based on differences in clinical phenotype,mutation,immune characteristics and differentially enriched pathways.Five prognosis-related genes were identified for prediction of survival of pancreatic cancer patients and to evaluate the efficacy of immunotherapy in various subtypes.展开更多
BACKGROUND mRNA vaccines have been investigated in multiple tumors,but limited studies have been conducted on their use for hepatocellular carcinoma(HCC).AIM To identify candidate mRNA vaccine antigens for HCC and sui...BACKGROUND mRNA vaccines have been investigated in multiple tumors,but limited studies have been conducted on their use for hepatocellular carcinoma(HCC).AIM To identify candidate mRNA vaccine antigens for HCC and suitable subpopu-lations for mRNA vaccination.METHODS Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome Atlas.Genes with somatic mutations and copy number variations were identified by cBioPortal analysis.The differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website analysis.The Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells(APCs).Tumor-associated antigens were overexpressed in tumors and associated with prognosis,genomic alterations,and APC infiltration.A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune subtypes.The weighted gene coexpression network analysis(WGCNA)was used to determine the candidate biomarker molecules for appropriate populations for mRNA vaccines.immune subtypes showed distinct cellular and clinical characteristics.The IS1 and IS3 immune subtypes were immunologically“cold”.The IS2 and IS4 immune subtypes were immunologically“hot”,and the immune checkpoint genes and immunogenic cell death genes were upregulated in these subtypes.IS1-related modules were identified with the WGCNA algorithm.Ultimately,five hub genes(RBP4,KNG1,METTL7A,F12,and ABAT)were identified,and they might be potential biomarkers for mRNA vaccines.CONCLUSION AURKA,CCNB1,CDC25C,CDK1,TRIP13,PES1,MCM3,PPM1G,NEK2,KIF2C,PTTG1,KPNA2,and PRC1 have been identified as candidate HCC antigens for mRNA vaccine development.The IS1 and IS3 immune subtypes are suitable populations for mRNA vaccination.RBP4,KNG1,METTL7A,F12,and ABAT are potential biomarkers for mRNA vaccines.展开更多
BACKGROUND Cellular senescence,a state of stable growth arrest,is intertwined with human cancers.However,characterization of cellular senescence-associated phenotypes in hepatocellular carcinoma(HCC)remains unexplored...BACKGROUND Cellular senescence,a state of stable growth arrest,is intertwined with human cancers.However,characterization of cellular senescence-associated phenotypes in hepatocellular carcinoma(HCC)remains unexplored.AIM To address this issue,we delineated cellular senescence landscape across HCC.METHODS We enrolled two HCC datasets,TCGA-LIHC and International Cancer Genome Consortium(ICGC).Unsupervised clustering was executed to probe tumor heterogeneity based upon cellular senescence genes.Least absolute shrinkage and selection operator algorithm were utilized to define a cellular senescence-relevant scoring system.TRNP1 expression was measured in HCCs and normal tissues through immunohistochemistry,immunoblotting and quantitative real-time polymerase chain reaction.The influence of TMF-regulated nuclear protein(TRNP)1 on HCC senescence and growth was proven via a series of experiments.RESULTS TCGA-LIHC patients were classified as three cellular senescence subtypes,named C1–3.The robustness and reproducibility of these subtypes were proven in the ICGC cohort.C2 had the worst overall survival,C1 the next,and C3 the best.C2 presented the highest levels of immune checkpoints,abundance of immune cells,and immunogenetic indicators.Thus,C2 might possibly respond to immunotherapy.C2 had the lowest somatic mutation rate,while C1 presented the highest copy number variations.A cellular senescence-relevant gene signature was generated,which can predict patient survival,and chemo-or immunotherapeutic response.Experimentally,it was proven that TRNP1 presented the remarkable upregulation in HCCs.TRNP1 knockdown induced apoptosis and senescence of HCC cells and attenuated tumor growth.CONCLUSION These findings provide a systematic framework for assessing cellular senescence in HCC,which decode the tumor heterogeneity and tailor the pharmacological interventions to improve clinical management.展开更多
BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by th...BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.展开更多
BACKGROUND Synchronous colorectal carcinomas(SCRC)are two or more primary colorectal carcinomas identified simultaneously or within 6 mo of the initial presentation in a single patient.Their incidence is low and the n...BACKGROUND Synchronous colorectal carcinomas(SCRC)are two or more primary colorectal carcinomas identified simultaneously or within 6 mo of the initial presentation in a single patient.Their incidence is low and the number of pathological types of SCRC is usually no more than two.It is very unusual that the pathological findings of a patient with SCRC show more than two different pathological subtypes.Here,we report a rare case of SCRC with three pathological subtypes.CASE SUMMARY A 75-year-old woman who had no previous medical history or family history was admitted to the hospital because of intermittent hematochezia for more than a month.Colonoscopy displayed an irregularly shaped neoplasm of the rectum,a tumor-like lesion causing intestinal stenosis in the descending colon,and a polypoidal neoplasm in the ileocecum.Subsequently,she underwent total colectomy,abdominoperineal resection for rectal cancer,and ileostomy.After operation,the pathological report showed three pathological subtypes including well-differentiated adenocarcinoma of the ascending colon,moderately differen-tiated adenocarcinoma of the descending colon,and mucinous adenocarcinoma of the rectum.She is now recovering well and continues to be closely monitored during follow-up.CONCLUSION Preoperative colonoscopy examination,imaging examination,and extensive intraoperative exploration play important roles in reducing the number of missed lesions.展开更多
BACKGROUND Risk stratification for patients with gastric precancerous lesions for endoscopic surveillance remains controversial.AIM To analysis of patients having developed gastric adenocarcinoma during the period of ...BACKGROUND Risk stratification for patients with gastric precancerous lesions for endoscopic surveillance remains controversial.AIM To analysis of patients having developed gastric adenocarcinoma during the period of follow-up.METHODS We conducted a retrospective study on patients having undergone upper endoscopy prior to the development of gastric adenocarcinoma. The presence and stage of precancerous lesions as well as subtype of intestinal metaplasia at the baseline endoscopy got evaluated. Literature mini-review was performed.RESULTS Out of 1681 subjects in the Biobank, gastric adenocarcinoma was detected in five cases in whom previous endoscopy data with biopsies either from the corpus or antral part were available. All of the patients had incomplete intestinal metaplasia during the baseline endoscopy;all three subjects in whom intestinal metaplasia subtyping was performed according to Filipe et al, had Type Ⅲ intestinal metaplasia. Two of the five cases had low Operative Link on Gastritis Assessment(OLGA) and Operative Link on Gastritis Intestinal Metaplasia Assessment(OLGIM) stages(Ⅰ-Ⅱ) at the baseline.CONCLUSION The presence of incomplete intestinal metaplasia, in particular, that of Type Ⅲ is a better predictor for gastric adenocarcinoma development than OLGA/OLGIM staging system. Subtyping of intestinal metaplasia have an important role in the risk stratification for surveillance decisions.展开更多
文摘Background: Breast cancer is a genetically and clinically heterogeneous disease with multiple subtypes. The classification of these subtypes has evolved over the years. The most common and widely accepted classification of breast cancer is from an immunohistochemical perspective, based on the expression of the following hormone receptors: Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor (HER2). Accordingly, the following four subtypes of breast cancer are widely recognized—Luminal A, Luminal B, HER2 Enriched and Triple Negative. Breast cancer management approaches include surgery, chemotherapy, radiotherapy and targeted hormone therapy necessitated by molecular subtyping. Aims: This study aimed to determine the level of adherence to breast cancer molecular subtyping among women with breast cancer attending tertiary health facilities in Imo State. Methodology: Immunohistochemistry reports of women with breast cancer attending tertiary health facilities in Imo State were retrieved from patient’s case files. Tissue blocks were also retrieved from tissue block archives of both hospitals for women who did not take up immunohistochemistry services after their initial diagnosis and also those whose immunohistochemistry reports were not found in their case files. Results: Among the 121 women that participated in the study, there were in all 74 (61.2%) had molecular subtyping of their tumour blocks. Up to 45 (37.2%) did not go for molecular subtyping of their tumour blocks while 2 (1.7%) were not sure whether they had or not. Conclusion: It, therefore, depicts that the rate of uptake was found as 61.2% among the participants and there is a need to create more awareness of the importance of molecular subtyping, which necessitates the use of targeted hormone therapy.
基金The study design,data collection,data analysis,manuscript preparation,and publication decisions of this work were supported by the Science and Technology Program of Zhejiang Province Traditional Chinese Medicine(2023ZL056,2023ZL409)the Foundation Project of Zhejiang Chinese Medical University(2022JKZKTS26,2022JKJNTZ16,2022JKJNTZ23).
文摘Background:Breast cancer is the most common cancer,and abnormal lipid metabolism is associated with cancer.APOD expression is negatively correlated with various cancers related to tumor prognosis.DNA methylation may affect APOD expression.Therefore,this paper aims to investigate the significance of APOD expression and APOD DNA methylation in breast cancer.Methods:This study utilized comprehensive bioinformatics analysis of APOD using Gene Expression database of Normal and Tumor tissues 2,UCSC Xena,etc.Clinical and survival information obtained from the The Cancer Genome Atlas and Gene Expression Omnibus datasets were extracted for data mining.Results:The correlation between APOD and breast cancer was examined,along with the connection between APOD DNA methylation and APOD expression.In the The Cancer Genome Atlas cohort,as well as GSE31448 and GSE65194 datasets,APOD expression decreased in breast cancer(P<0.0001).Clinical feature analysis results showed that APOD expression was correlated with the PAM50 subtype,with the lowest expression in the Basal subtype(P<0.0001).High APOD expression is a good prognostic marker for breast cancer(HR=0.71,P=0.037).APOD methylation level was significantly negatively correlated with expression level(R=−0.4770,P<0.001),and cg15231202,cg23720929,and cg05624196 were important regulatory targets.High APOD expression was associated with higher metabolism and extracellular matrix scores.Conclusion:APOD is an independent prognostic marker for breast cancer and is regulated by DNA methylation to modulate mRNA expression.
文摘Listeria monocytogenes,one of the most important foodborne pathogens,can cause listeriosis,a lethal disease for humans.L.ivanovii,which is closely related to L.monocytogenes,is also widely distributed in nature and infects mainly warm-blooded ruminants,causing economic loss.Thus,there are high priority needs for methodologies for rapid,specific,cost-effective and accurate detection,characterization and subtyping of L.monocytogenes and L.ivanovii in foods and environmental sources.In this review,we(A)described L.monocytogenes and L.ivanovii,world-wide incidence of listeriosis,and prevalence of various L.monocytogenes strains in food and environmental sources;(B)comprehensively reviewed different types of traditional and newly developed methodologies,including culture-based,antigen/antibody-based,LOOP-mediated isothermal amplification,matrix-assisted laser desorption ionization-time of flight-mass spectrometry,DNA microarray,and genomic sequencing for detection and characterization of L.monocytogenes in foods and environmental sources;(C)comprehensively summarized different subtyping methodologies,including pulsed-field gel electrophoresis,multi-locus sequence typing,ribotyping,and phage-typing,and whole genomic sequencing etc.for subtyping of L.monocytogenes strains from food and environmental sources;and(D)described the applications of these methodologies in detection and subtyping of L.monocytogenes in foods and food processing facilities.
文摘Objective To analyze the value of multi-slice spiral CT ( SCT) scan in staging and subtyping of renal cell carcinoma ( RCC) . Methods The preoperative kidney SCT data and postoperative pathology results of 64 patients with RCC were retrospectively analyzed. The pa-
文摘The prevalence of type 2 diabetes mellitus(T2DM)is increasing rapidly worldwide.Because of the limited success of generic interventions,the focus of the disease study has shifted toward personalized strategies,particularly in the early stages of the disease.Traditional Chinese medicine(TCM)is based on a systems view combined with personalized strategies and has improved our knowledge of personalized diagnostics.From a systems biology perspective,the understanding of personalized diagnostics can be improved to yield a biochemical basis for such strategies;for example,metabolomics can be used in combination with other system-based diagnostic methods such as ultra-weak photon emission(UPE).In this study,we investigated the feasibility of using plasma metabolomics obtained from 44 pre-T2DM subjects to stratify the following TCM-based subtypes:Qi-Yin deficiency,Qi-Yin deficiency with dampness,and Qi-Yin deficiency with stagnation.We studied the relationship between plasma metabolomics and UPE with respect to TCM-based subtyping in order to obtain biochemical information for further interpreting disease subtypes.Principal component analysis of plasma metabolites revealed differences among the TCM-based pre-T2DM subtypes.Relatively high levels of lipids(e.g.,cholesterol esters and triglycerides)were important discriminators of two of the three subtypes and may be associated with a higher risk of cardiovascular disease.Plasma metabolomics data indicate that the lipid profile is an essential component captured by UPE with respect to stratifying subtypes of T2DM.The results suggest that metabolic differences exist among different TCM-based subtypes of pre-T2DM,and profiling plasma metabolites can be used to discriminate among these subtypes.Plasma metabolomics thus provides biochemical insights into system-based UPE measurements.
基金financially supported by the Scientific Project Unit of Erzincan University(Project No:SAG-A-240215-0128).
文摘Objective:To investigate Blastocystis’etiologic role and association with gastrointestinal symptomatology in acute and chronic urticaria patients and to identify Blastocystis subtypes responsible for urticaria.Methods:The study included urticaria patients and healthy individuals that presented to our polyclinic between June 2015 and May 2017.The participants were assigned into Group栺(137 patients),subdivided into acute(72)and chronic urticaria patients(65),and Group栻(129 control individuals).Blastocystis presence was investigated by native-Lugol examination,trichrome staining,PCR using sequence tagged site primers,and DNA sequencing analysis.The phylogenetic tree was constructed.Results:The native-Lugol and trichrome staining methods revealed that 16 patients(16/133,12.0%)had Blastocystis-positive stool samples,of which seven samples(7/133,5.3%)belonged acute and nine(9/133,6.8%)to chronic urticaria patients.Concerning Blastocystis subtypes,of the acute urticaria patients,three had subtype 1(ST1),one had ST2,and three had ST3.Of the chronic urticaria patients,one had ST1 and eight had ST3.Blastocystis positivity was detected in two control individuals(2/123,1.6%),both being ST3.All subtypes identified by PCR were confirmed by the sequencing analysis.The acute and chronic urticaria groups showed no statistically significant differences for Blastocystis positivity(P=0.60)and subtype distribution(P=0.15).A statistically significant difference was found between the urticaria patients and the controls for Blastocystis positivity(P<0.01),but not for subtype distribution(P=0.67)or for Blastocystis presence and gastrointestinal complaints.Conclusions:This study on Blastocystis subtype distribution among Turkish urticaria patients showed results consistent with the literature.It was concluded that Blastocystis should be kept in mind in patients with urticaria.
基金This work was supported in part by the grant from the National Science and Technology Major Project of China(No.2017ZX10203205)the Science Foundation of Zhejiang province(LQ18H160006).
文摘Hepatocellular carcinoma(HCC)is one of the most prevalent and fatal digestive tumors.Treatment for this disease has been constraint by heterogeneity of this group of tumors,which has greatly limited the progress in personalized therapy.Although existing studies have revealed the genetic and epigenetic blueprints that drive HCCs,many of the molecular mechanisms that lead to HCCs remain elusive.Recent advances in techniques for studying functional genomics,such as genome sequencing and transcriptomic analyses,have led to the discovery of molecular mechanisms that participate in the initiation and evolution of HCC.Integrative multi-omics analyses have identified several molecular subtypes of HCC associated with specific molecular characteristics and clinical outcomes.Deciphering similar molecular features among highly heterogeneous HCC patients is a prerequisite to implementation of personalized therapeutics.This review summarizes the current research progresses in precision therapy on the backbone of molecular subtypes of HCC.
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.
基金Supported by Zhejiang Provincial Natural Science Foundation of China,No.LTGY23H180017Medical Science and Technology Project of Zhejiang Province,No.2023KY503.
文摘BACKGROUND Macrotrabecular-massive hepatocellular carcinoma(MTM-HCC)is closely related to aggressive phenotype,gene mutation,carcinogenic pathway,and immunohistochemical markers and is a strong independent predictor of early recurrence and poor prognosis.With the development of imaging technology,successful applications of contrast-enhanced magnetic resonance imaging(MRI)have been reported in identifying the MTM-HCC subtype.Radiomics,as an objective and beneficial method for tumour evaluation,is used to convert medical images into high-throughput quantification features that greatly push the development of precision medicine.AIM To establish and verify a nomogram for preoperatively identifying MTM-HCC by comparing different machine learning algorithms.METHODS This retrospective study enrolled 232(training set,162;test set,70)hepatocellular carcinoma patients from April 2018 to September 2021.A total of 3111 radiomics features were extracted from dynamic contrast-enhanced MRI,followed by dimension reduction of these features.Logistic regression(LR),K-nearest neighbour(KNN),Bayes,Tree,and support vector machine(SVM)algorithms were used to select the best radiomics signature.We used the relative standard deviation(RSD)and bootstrap methods to quantify the stability of these five algorithms.The algorithm with the lowest RSD represented the best stability,and it was used to construct the best radiomics model.Multivariable logistic analysis was used to select the useful clinical and radiological features,and different predictive models were established.Finally,the predictive performances of the different models were assessed by evaluating the area under the curve(AUC).RESULTS The RSD values based on LR,KNN,Bayes,Tree,and SVM were 3.8%,8.6%,4.3%,17.7%,and 17.4%,respectively.Therefore,the LR machine learning algorithm was selected to construct the best radiomics signature,which performed well with AUCs of 0.766 and 0.739 in the training and test sets,respectively.In the multivariable analysis,age[odds ratio(OR)=0.956,P=0.034],alphafetoprotein(OR=10.066,P<0.001),tumour size(OR=3.316,P=0.002),tumour-to-liver apparent diffusion coefficient(ADC)ratio(OR=0.156,P=0.037),and radiomics score(OR=2.923,P<0.001)were independent predictors of MTM-HCC.Among the different models,the predictive performances of the clinical-radiomics model and radiological-radiomics model were significantly improved compared to those of the clinical model(AUCs:0.888 vs 0.836,P=0.046)and radiological model(AUCs:0.796 vs 0.688,P=0.012),respectively,in the training set,highlighting the improved predictive performance of radiomics.The nomogram performed best,with AUCs of 0.896 and 0.805 in the training and test sets,respectively.CONCLUSION The nomogram containing radiomics,age,alpha-fetoprotein,tumour size,and tumour-to-liver ADC ratio revealed excellent predictive ability in preoperatively identifying the MTM-HCC subtype.
基金Supported by the National Natural Science Foundation of China,No. 81860431 and 82060447the Jiangxi Natural Science Foundation,No. 20181BBG70025
文摘BACKGROUND Intraductal papillary neoplasm of the bile duct(IPNB)is a rare distinct subtype of precursor lesions of biliary carcinoma.IPNB is considered to originate from luminal biliary epithelial cells,typically displays mucin-hypersecretion or a papillary growth pattern,and results in cystic dilatation[1].IPNB develops anywhere in the intrahepatic and extrahepatic biliary tracts,and can occur in various pathological stages from low-grade dysplasia to invasive carcinoma.IPNBs have similar phenotypic changes in the occurrence and development of all subtypes,and the prognosis is significantly better than that of traditional(nonpapillary)cholangiocarcinoma.AIM To evaluate the clinicopathological features of IPNB to provide evidence-based guidance for treatment.METHODS Invasive IPNB,invasive intraductal papillary mucinous neoplasm of the pancreas(IPMN),and traditional cholangiocarcinoma data for affected individuals from 1975 to 2016 were obtained from the Surveillance,Epidemiology,and End Results(SEER)database.Annual percentage changes(APCs)in the incidence and incidence-based(IB)mortality were calculated.We identified the independent predictors of overall survival(OS)and cancer-specific survival(CSS)in indivi duals with invasive IPNB.RESULTS The incidence and IB mortality of invasive IPNB showed sustained decreases,with an APC of-4.5%(95%CI:-5.1%to-3.8%)and-3.3%(95%CI:-4.1%to-2.6%)(P<0.001),respectively.Similar decreases in incidence and IB mortality were seen for invasive IPMN but not for traditional cholangiocarcinoma.Both OS and CSS for invasive IPNB were better than for invasive IPMN and traditional cholangiocarcinoma.A total of 1635 individuals with invasive IPNB were included in our prognosis analysis.The most common tumor sites were the pancreaticobiliary ampulla(47.9%)and perihilar tract(36.7%),but the mucin-related subtype of invasive IPNB was the main type,intrahepatically(approximately 90%).In the univariate and multivariate Cox regression analysis,age,tumor site,grade and stage,subtype,surgery,and chemotherapy were associated with OS and CSS(P<0.05).CONCLUSION Incidence and IB mortality of invasive IPNB trended steadily downward.The heterogeneity of IPNB comprises site and the tumor’s mucin-producing status.
基金supported by the National Natural Science Foundation of China (31970696, 81502975, 82188102, and 81830089)Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar (LR22H160010)+2 种基金National Key Research and Development Program of China (2019YFC1316000)Zhejiang Provincial Key Research and Development Program (2019C03019)Zhejiang Provincial College Student Science and Technology Innovation Activity Plan-College Student Innovation and Entrepreneurship Incubation Program (Young Talent Program)(2022R40122)
文摘Pancreatic cancer is characterized by inter-tumoral and intra-tumoral heterogeneity,especially in genetic alteration and microenvironment.Conventional therapeutic strategies for pancreatic cancer usually suffer resistance,highlighting the necessity for personalized precise treatment.Cancer vaccines have become promising alternatives for pancreatic cancer treatment because of their multifaceted advantages including multiple targeting,minimal nonspecific effects,broad therapeutic window,low toxicity,and induction of persistent immunological memory.Multiple conventional vaccines based on the cells,microorganisms,exosomes,proteins,peptides,or DNA against pancreatic cancer have been developed;however,their overall efficacy remains unsatisfactory.Compared with these vaccine modalities,messager RNA(mRNA)-based vaccines offer technical and conceptional advances in personalized precise treatment,and thus represent a potentially cutting-edge option in novel therapeutic approaches for pancreatic cancer.This review summarizes the current progress on pancreatic cancer vaccines,highlights the superiority of mRNA vaccines over other conventional vaccines,and proposes the viable tactic for designing and applying personalized mRNA vaccines for the precise treatment of pancreatic cancer.
基金supported by the National Institutes of Health(R01EY027920:Cellular and Molecular Mechanisms that Contribute to Pressure-Induced Retinal Inflammation to DK),EY027920Molecular mechanisms of mechanotransduction in the aqueous outflow pathway(to DK),T32EY024234+3 种基金Vision Research Training award(to JMB and CNR),P30EY014800Vision Core Grant at the University of Utah(to DK)Stauss-Rankin Foundation(to DK)an Unrestricted Grant from Research to Prevent Blindness to the Department of Ophthalmology at the University of Utah。
文摘Mechanical forces shape the development,function,and survival of every cell within the central nervous system(CNS)but are particularly important for astroglia,a subtype of glial cell that mediates communication between neurons and blood vessels.
基金supported by the National Natural Science Foundation of China(31970696,81502975,81830089,U20A20378,82188102)the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(LR22H160010)+2 种基金the National Key Research and Development Program(2019YFC1316000)the Zhejiang Provincial Key Research and Development Program(2019C03019)the Zhejiang Provincial College Student Science and Technology Innovation Activity Plan-College Student Innovation and Entrepreneurship Incubation Program(Young Talent Program)(2022R40122)。
文摘Cholangiocarcinoma(CHOL)is one of the most aggressive tumors worldwide and cannot be effectively treated by conventional and novel treatments,including immune checkpoint blockade therapy.The mRNA vaccine-based immunotherapeutic strategy has attracted much attention for various diseases,however,its application in CHOL is limited due to the thoughtlessness in the integration of vaccine design and patient selection.A recent study established an integrated path for identifying potent CHOL antigens for mRNA vaccine development and a precise stratification for identifying CHOL patients who can benefit from the mRNA vaccines.In spite of a promising prospect,further investigations should identify immunogenic antigens and onco-immunological characteristics of CHOL to guide the clinical application of CHOL mRNA vaccines in the future.
基金supported by grants from the 2021 Graduate Education Innovation Program Project of Guangxi Zhuang Autonomous Region [YCBZ2021041]the National innovative training program for college students [202100001580]grants from the National Natural Science Foundation of China [NSFC,31860040]。
文摘Objective This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance(HIVDR)in patients with ART failure from 2014 to 2020 in Hainan,China.Methods A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan.We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences.Drug resistance mutations(DRMs)were analyzed using the Stanford University HIV Drug Resistance Database.Results A total of 307 HIV-infected patients with ART failure were included,and 241 available pol sequences were obtained.Among 241 patients,CRF01_AE accounted for 68.88%,followed by CRF07_BC(17.00%)and eight other subtypes(14.12%).The overall prevalence of HIVDR was 61.41%,and the HIVDR against non-nucleoside reverse transcriptase inhibitors(NNRTIs),nucleotide reverse transcriptase inhibitors(NRTIs),and protease inhibitors(PIs)were 59.75%,45.64%,and 2.49%,respectively.Unemployed patients,hypoimmunity or opportunistic infections in individuals,and samples from 2017 to 2020 increased the odd ratios of HIVDR.Also,HIVDR was less likely to affect female patients.The common DRMs to NNRTIs were K103N(21.99%)and Y181C(20.33%),and M184V(28.21%)and K65R(19.09%)were the main DRMs against NRTIs.Conclusion The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.
文摘Pancreatic cancer is associated with high mortality and is one of the most aggressive of malignancies,but studies have not fully evaluated its molecular subtypes,prognosis and response to immunotherapy of different subtypes.The purpose of this study was to explore the molecular subtypes and the key genes associated with the prognosis of pancreas cancer patients and study the clinical phenotype,prognosis and response to immunotherapy using single-cell seq data and bulk RNA seq data,and data retrieved from GEO and TCGA databases.Methods:Single-cell seq data and bioinformatics methods were used in this study.Pancreatic cancer data were retrieved from GEO and TCGA databases,the molecular subtypes of pancreatic cancer were determined using the six cGAS-STING related pathways,and the clinical phenotype,mutation,immunological characteristics and pathways related to pancreatic cancer were evaluated.Results:Pancreatic cancer was classified into 3 molecular subtypes,and survival analysis revealed that patients in Cluster3(C3)had the worst prognosis,whereas Cluster1(C1)had the best prognosis.The clinical phenotype and gene mutation were statistically different among the three molecular subtypes.Analysis of immunotherapy response revealed that most immune checkpoint genes were differentially expressed in the three subtypes.A lower risk of immune escape was observed in Cluster1(C1),indicating higher sensitivity to immunotherapeutic drugs and subjects in this Cluster are more likely to benefit from immunotherapy.The pathways related to pancreatic cancer were differentially enriched among the three subtypes.Five genes,namely SFRP1,GIPR,EMP1,COL17A and CXCL11 were selected to construct a prognostic signature.Conclusions:Single-cell seq data were to classify pancreatic cancer into three molecular subtypes based on differences in clinical phenotype,mutation,immune characteristics and differentially enriched pathways.Five prognosis-related genes were identified for prediction of survival of pancreatic cancer patients and to evaluate the efficacy of immunotherapy in various subtypes.
文摘BACKGROUND mRNA vaccines have been investigated in multiple tumors,but limited studies have been conducted on their use for hepatocellular carcinoma(HCC).AIM To identify candidate mRNA vaccine antigens for HCC and suitable subpopu-lations for mRNA vaccination.METHODS Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome Atlas.Genes with somatic mutations and copy number variations were identified by cBioPortal analysis.The differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website analysis.The Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells(APCs).Tumor-associated antigens were overexpressed in tumors and associated with prognosis,genomic alterations,and APC infiltration.A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune subtypes.The weighted gene coexpression network analysis(WGCNA)was used to determine the candidate biomarker molecules for appropriate populations for mRNA vaccines.immune subtypes showed distinct cellular and clinical characteristics.The IS1 and IS3 immune subtypes were immunologically“cold”.The IS2 and IS4 immune subtypes were immunologically“hot”,and the immune checkpoint genes and immunogenic cell death genes were upregulated in these subtypes.IS1-related modules were identified with the WGCNA algorithm.Ultimately,five hub genes(RBP4,KNG1,METTL7A,F12,and ABAT)were identified,and they might be potential biomarkers for mRNA vaccines.CONCLUSION AURKA,CCNB1,CDC25C,CDK1,TRIP13,PES1,MCM3,PPM1G,NEK2,KIF2C,PTTG1,KPNA2,and PRC1 have been identified as candidate HCC antigens for mRNA vaccine development.The IS1 and IS3 immune subtypes are suitable populations for mRNA vaccination.RBP4,KNG1,METTL7A,F12,and ABAT are potential biomarkers for mRNA vaccines.
文摘BACKGROUND Cellular senescence,a state of stable growth arrest,is intertwined with human cancers.However,characterization of cellular senescence-associated phenotypes in hepatocellular carcinoma(HCC)remains unexplored.AIM To address this issue,we delineated cellular senescence landscape across HCC.METHODS We enrolled two HCC datasets,TCGA-LIHC and International Cancer Genome Consortium(ICGC).Unsupervised clustering was executed to probe tumor heterogeneity based upon cellular senescence genes.Least absolute shrinkage and selection operator algorithm were utilized to define a cellular senescence-relevant scoring system.TRNP1 expression was measured in HCCs and normal tissues through immunohistochemistry,immunoblotting and quantitative real-time polymerase chain reaction.The influence of TMF-regulated nuclear protein(TRNP)1 on HCC senescence and growth was proven via a series of experiments.RESULTS TCGA-LIHC patients were classified as three cellular senescence subtypes,named C1–3.The robustness and reproducibility of these subtypes were proven in the ICGC cohort.C2 had the worst overall survival,C1 the next,and C3 the best.C2 presented the highest levels of immune checkpoints,abundance of immune cells,and immunogenetic indicators.Thus,C2 might possibly respond to immunotherapy.C2 had the lowest somatic mutation rate,while C1 presented the highest copy number variations.A cellular senescence-relevant gene signature was generated,which can predict patient survival,and chemo-or immunotherapeutic response.Experimentally,it was proven that TRNP1 presented the remarkable upregulation in HCCs.TRNP1 knockdown induced apoptosis and senescence of HCC cells and attenuated tumor growth.CONCLUSION These findings provide a systematic framework for assessing cellular senescence in HCC,which decode the tumor heterogeneity and tailor the pharmacological interventions to improve clinical management.
基金Supported by the German Federal Ministry of Education and Research(BMBF-Wachstumskern-PRAEMED.BIO),03WKDB2Csupported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences,BO/00232/17/5+1 种基金Research Grants of National Research Development and Innovation Office,K115818/2015/1New National Excellence Program of the Ministry of Human Capacities,ÚNKP-18-4 Bolyai Plus.
文摘BACKGROUND Defective neutrophil regulation in inflammatory bowel disease(IBD)is thought to play an important role in the onset or manifestation of IBD,as it could lead to damage of the intestinal mucosal barrier by the infiltration of neutrophils in the inflamed mucosa and the accumulation of pathogens.Like neutrophils in the context of innate immune responses,immunoglobulin A(IgA)as an acquired immune response partakes in the defense of the intestinal epithelium.Under normal conditions,IgA contributes to the elimination of microbes,but in connection with the loss of tolerance to chitinase 3-like 1(CHI3L1)in IBD,IgA could participate in CHI3L1-mediated improved adhesion and invasion of potentially pathogenic microorganisms.The tolerance brake to CHI3L1 and the occurrence of IgA autoantibodies to this particular target,the exact role and underlying mechanisms of CHI3L1 in the pathogenesis of IBD are still unclear.AIM To determine the predictive potential of Ig subtypes of a novel serological marker,anti-CHI3L1 autoantibodies(aCHI3L1)in determining the disease phenotype,therapeutic strategy and long-term disease course in a prospective referral cohort of adult IBD patients.METHODS Sera of 257 Crohn’s disease(CD)and 180 ulcerative colitis(UC)patients from a tertiary IBD referral center of Hungary(Division of Gastroenterology,Department of Internal Medicine,Faculty of Medicine,University of Debrecen)were assayed for IgG,IgA,and secretory IgA(sIgA)type aCHI3L1 by enzyme-linked immunosorbent assay using recombinant CHI3L1,along with 86 healthy controls(HCONT).RESULTS The IgA type was more prevalent in CD than in UC(29.2%vs 11.1%)or HCONT(2.83%;P<0.0001 for both).However,sIgA subtype aCHI3L1 positivity was higher in both CD and UC patients than in HCONT(39.3%and 32.8%vs 4.65%,respectively;P<0.0001).The presence of both IgA and sIgA aCHI3L1 antibodies was associated with colonic involvement(P<0.0001 and P=0.038,respectively)in patients with CD.Complicated disease behavior at sample procurement was associated with aCHI3L1 sIgA positivity(57.1%vs 36.0%,P=0.009).IgA type aCH3L1 was more prevalent in patients with frequent relapse during the disease course in the CD group(46.9%vs 25.7%,P=0.005).In a group of patients with concomitant presence of pure inflammatory luminal disease and colon involvement at the time of diagnosis,positivity for IgA or sIgA type aCH3L1 predicted faster progression towards a complicated disease course in time-dependent models.This association disappeared after merging subgroups of different disease locations.CONCLUSION CHI3L1 is a novel neutrophil autoantigenic target in IBD.The consideration of antibody classes along with location-based prediction may transform the future of serology in IBD.
文摘BACKGROUND Synchronous colorectal carcinomas(SCRC)are two or more primary colorectal carcinomas identified simultaneously or within 6 mo of the initial presentation in a single patient.Their incidence is low and the number of pathological types of SCRC is usually no more than two.It is very unusual that the pathological findings of a patient with SCRC show more than two different pathological subtypes.Here,we report a rare case of SCRC with three pathological subtypes.CASE SUMMARY A 75-year-old woman who had no previous medical history or family history was admitted to the hospital because of intermittent hematochezia for more than a month.Colonoscopy displayed an irregularly shaped neoplasm of the rectum,a tumor-like lesion causing intestinal stenosis in the descending colon,and a polypoidal neoplasm in the ileocecum.Subsequently,she underwent total colectomy,abdominoperineal resection for rectal cancer,and ileostomy.After operation,the pathological report showed three pathological subtypes including well-differentiated adenocarcinoma of the ascending colon,moderately differen-tiated adenocarcinoma of the descending colon,and mucinous adenocarcinoma of the rectum.She is now recovering well and continues to be closely monitored during follow-up.CONCLUSION Preoperative colonoscopy examination,imaging examination,and extensive intraoperative exploration play important roles in reducing the number of missed lesions.
文摘BACKGROUND Risk stratification for patients with gastric precancerous lesions for endoscopic surveillance remains controversial.AIM To analysis of patients having developed gastric adenocarcinoma during the period of follow-up.METHODS We conducted a retrospective study on patients having undergone upper endoscopy prior to the development of gastric adenocarcinoma. The presence and stage of precancerous lesions as well as subtype of intestinal metaplasia at the baseline endoscopy got evaluated. Literature mini-review was performed.RESULTS Out of 1681 subjects in the Biobank, gastric adenocarcinoma was detected in five cases in whom previous endoscopy data with biopsies either from the corpus or antral part were available. All of the patients had incomplete intestinal metaplasia during the baseline endoscopy;all three subjects in whom intestinal metaplasia subtyping was performed according to Filipe et al, had Type Ⅲ intestinal metaplasia. Two of the five cases had low Operative Link on Gastritis Assessment(OLGA) and Operative Link on Gastritis Intestinal Metaplasia Assessment(OLGIM) stages(Ⅰ-Ⅱ) at the baseline.CONCLUSION The presence of incomplete intestinal metaplasia, in particular, that of Type Ⅲ is a better predictor for gastric adenocarcinoma development than OLGA/OLGIM staging system. Subtyping of intestinal metaplasia have an important role in the risk stratification for surveillance decisions.
