Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations...Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.展开更多
Background:Long non-coding RNAs(lncRNAs)act as epigenetic regulators for tumor hallmarks.This investigation sought to probe the carcinogenic trait of PAN3-AS1 across pan-cancer comprehensively.Methods:We studied the d...Background:Long non-coding RNAs(lncRNAs)act as epigenetic regulators for tumor hallmarks.This investigation sought to probe the carcinogenic trait of PAN3-AS1 across pan-cancer comprehensively.Methods:We studied the diagnostic and prognostic features and the immune landscape of PAN3-AS1 across pan-cancer by bioinformatics approaches.The hierarchical regulatory networks governing PAN3-AS1 expression in colon cancer were explored via chromatin immunoprecipitation,luciferase activity assays,and RNA immunoprecipitation,etc.We screened drugs sensitive to WAP four-disulfide core domain 13(WFDC13)by virtual screening and molecular docking.Results:Single-cell transcriptomics demonstrated that a variety of immune populations abnormally expressed PAN3-AS1 beyond tumor cells.Integration of data from multiple databases revealed that PAN3-AS1 was highly expressed and associated with a bad prognosis in various malignancies.Notably,PAN3-AS1 expression was correlated with a suppressive immune microenvironment.Moreover,we observed poor immunotherapy efficacy when PAN3-AS1 was highly expressed in melanoma.In vitro assays and functional enrichment analysis revealed that PAN3-AS1 was associated with cell proliferation and the immune response in colon cancer.Our experiments confirmed that PAN3-AS1 facilitated WFDC13 expression through competitive binding to hsa-miR-423-5p in colon cancer.Moreover,the present paper illustrated that enhancer activity exerts an important modulatory ability for PAN3-AS1 expression.Conclusion:In short,PAN3-AS1 is a valuable biomarker for diagnosis and prognosis.PAN3-AS1 exhibits linkage to a cold tumor immune microenvironment(TME)and forecasts durable benefit from immunotherapy.Addressing the PAN3-AS1/miR-423-5p/WFDC13 axis might provide a novel option for improving immunotherapy efficacy in colon cancer.展开更多
BACKGROUND Ectonucleoside triphosphate diphosphohydrolase 6(ENTPD6),a member of the ENTPD family,has been implicated in certain cancers,yet a comprehensive analysis across multiple cancer types remains lacking.AIM To ...BACKGROUND Ectonucleoside triphosphate diphosphohydrolase 6(ENTPD6),a member of the ENTPD family,has been implicated in certain cancers,yet a comprehensive analysis across multiple cancer types remains lacking.AIM To systematically evaluate ENTPD6’s expression,prognostic significance,and functions across multiple cancer types.METHODS In this study,we performed a pan-cancer analysis to investigate the correlation between ENTPD6 expression and various factors,including prognosis,genetic alterations,epigenetic modification,immune infiltration,immunotherapy responses,functional enrichment,and drug sensitivity.A tissue microarray of gastrointestinal tumors was used to validate differential ENTPD6 protein expression.RESULTS Pan-cancer analysis revealed that ENTPD6 expression was significantly elevated in many cancers.Immunohistochemistry staining analysis revealed that ENTPD6 expression was significantly higher in esophageal carcinoma,stomach adenocarcinoma,colon adenocarcinoma,rectal adenocarcinoma,and pancreatic adenocarcinoma compared to normal tissues.Furthermore,ENTPD6 expression was strongly associated with immune-infiltrating cells,particularly clusters of differentiation 8+T cells and natural killer cells,and correlated with immune-related genomic features including tumor mutational burden and microsatellite instability.Pathway analysis indicated that ENTPD6 expression was primarily linked to purine and pyrimidine metabolism pathways.Drug sensitivity analysis revealed that high ENTPD6 expression was sensitive to RDEA119,selumetinib,and PD-0325901.CONCLUSION This pan-cancer study elucidates the pivotal role of ENTPD6 in tumor progression and establishes its potential as a therapeutic target for immunotherapeutic approaches in specific malignancies.展开更多
Background:NDC80 is pivotal in cell division,particularly in regulating the G2/M transition and mitotic progression.Recent studies have demonstrated that NDC80 is significantly overexpressed in multiple solid tumors.F...Background:NDC80 is pivotal in cell division,particularly in regulating the G2/M transition and mitotic progression.Recent studies have demonstrated that NDC80 is significantly overexpressed in multiple solid tumors.Further analysis has suggested that its high expression is significantly associated with an elevated pathological grade,increased metastatic risk,and shortened overall survival in patients with cancer.However,its precise role in pan-cancer development,progression,and prognosis remains unclear.Methods:We conducted a multi-omics analysis of NDC80 using genomic,transcriptomic,and proteomic data from 33 cancer types in The Cancer Genome Atlas,Clinical Proteomic Tumor Analysis Consortium,Genotype-Tissue Expression,and Human Protein Atlas.Results:The results demonstrated frequent NDC80 mutations across multiple malignancies and significantly elevated expression in tumor tissues compared with that in their normal counterparts,correlating with worse overall and disease-free survival.Moreover,NDC80 expression was strongly associated with oncogenic pathways,key protein regulators,cellular components,myeloid-derived suppressor cell infiltration,ESTIMATE scores,and cancer-related signaling networks.Conclusions:These findings underscore the potential of NDC80 as a prognostic biomarker and therapeutic target for cancer treatment.展开更多
Background:Rho GDP dissociation inhibitor 2(ARHGDIB),a key regulator of Rho GTPase,plays a significant role in the onset and progression of cancer by participating in various biological processes.However,the diverse b...Background:Rho GDP dissociation inhibitor 2(ARHGDIB),a key regulator of Rho GTPase,plays a significant role in the onset and progression of cancer by participating in various biological processes.However,the diverse biological roles of ARHGDIB across pan-cancer remain systematically and comprehensively unexplored.We aimed to elucidate the diagnostic and prognostic roles of ARHGDIB and its potential tumor-related mechanisms in human cancers,using bioinformatics approaches.Methods:Data on 33 tumor types were downloaded from The Cancer Genome Atlas,and R software was used to statistically analyze ARHGDIB expression levels and prognostic significance across pan-cancer.Western blot was used to verify the protein expression of ARHGDIB in breast cancer and liver cancer cell lines.Additionally,various databases,including UALCAN,GEPIA,cBioPortal,TIMER,CancerSEA,GSCALite,and GSEA,were used to examine ARHGDIB protein expression across pan-cancer,its correlation with tumor pathological staging,ARHGDIB mutation types and frequencies,and immune cell infiltration.Furthermore,functional analyses at the single-cell level,drug sensitivity assessments,and explorations of related signaling pathways were performed.Results:ARHGDIB exhibits abnormal expression at mRNA and protein levels across various cancers.Western blot results show that ARHGDIB is highly expressed in breast cancer and liver cancer cells.ARHGDIB influences the prognosis of lower-grade glioma,bladder cancer,sarcoma,and skin cutaneous melanoma.It exhibits the highest frequency of gene alterations in uterine carcinosarcoma,primarily characterized by gene amplification.Additionally,ARHGDIB is strongly associated with immune-infiltrating cells and immune checkpoints in the tumor microenvironment.It potentially influences cancer progression through multiple signaling pathways.Conclusions:ARHGDIB is a potential prognostic marker in various cancers and a crucial regulator of the tumor microenvironment.It represents a promising therapeutic target by modulating cancer progression through multiple biological behaviors and signaling pathways.展开更多
Background:The nuclear receptor coactivator(NCOA)family,including NCOA1,NCOA2,and NCOA3,is critical in regulating gene expression through interactions with nuclear receptors and other transcription factors.These coact...Background:The nuclear receptor coactivator(NCOA)family,including NCOA1,NCOA2,and NCOA3,is critical in regulating gene expression through interactions with nuclear receptors and other transcription factors.These coactivators are implicated in various cancers,but their comprehensive roles across different cancer types remain poorly understood.Methods:We performed a pan-cancer bioinformatics analysis using data from The Cancer Genome Atlas and the Genotype-Tissue Expression project.We assessed the differential expression,copy number variations,mutations,methylation status,tumor mutation burden,microsatellite instability,and immune cell infiltration associated with NCOA family members across various cancers.Differential expression analysis was conducted using the DESeq2 package.Methylation data were analyzed using the ChAMP package,and immune cell infiltration was estimated using the CIBERSORT algorithm.Results:NCOA1 and NCOA2 were predominantly downregulated in multiple cancers,suggesting potential tumor suppressor roles,whereas NCOA3 was largely upregulated,indicating a consistent oncogenic function.These expression patterns significantly correlated with patient prognosis.Frequent copy number variations,particularly gains,and high mutation rates were observed in NCOA2.NCOA3 demonstrated consistent hypomethylation in tumors,which was associated with increased gene expression.Significant correlations were found between NCOA expression and tumor mutation burden,microsatellite instability,and immune cell infiltration,indicating their involvement in genomic instability and immune modulation.Conclusion:This comprehensive analysis reveals significant alterations in the expression,genomic,and epigenetic profiles of NCOA family members across various cancers.The findings highlight the multifaceted roles of NCOA1,NCOA2,and NCOA3 in tumorigenesis and their potential as biomarkers and therapeutic targets.Future research should focus on elucidating the mechanisms underlying the associations between NCOA expression,genomic alterations,and immune modulation to develop targeted cancer therapies.展开更多
Accumulating evidence in recent years indicates that DNA methylation(5-methyl-2-deoxycytidine,5-mdC) and hydroxymethylation(5-hydroxymethyl-2-deoxycytidine, 5-hmd C) have been implicated in various biological processe...Accumulating evidence in recent years indicates that DNA methylation(5-methyl-2-deoxycytidine,5-mdC) and hydroxymethylation(5-hydroxymethyl-2-deoxycytidine, 5-hmd C) have been implicated in various biological processes, and the aberrations of these DNA cytosine modifications is tightly associated with cancer. N6-methyl-2-deoxyadenosine(m~6dA), as a newly discovered epigenetic modification in genome of mammals, has been demonstrated to play vital regulatory roles in tumorigenesis. However, the content information of m~6dA in human tumor tissues is still limited and pan-cancer analysis of these DNA epigenetic modifications is lacked. Herein, we developed a sensitive and robust stable isotopediluted hydrophilic interaction liquid chromatography-tandem mass spectrometry(HILIC-MS/MS) method for accurate quantification of m~6dA, 5-mdC and 5-hmdC in genomic DNA from 82 pairs of human tumor tissues and matched tumor-adjacent normal tissues. The types of tumors included esophagus cancer, lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, stromal tumor and colorectal cancer.Compared to the normal tissues, we revealed the level of m6dA was increased in tumor tissues of esophagus cancer, lung cancer and liver cancer, whereas the level of m~6dA was diminished in tumor tissues of pancreatic cancer and gastric cancer;while the contents of 5-mdC and 5-hmdC exhibited significant decrease in tumor tissues of most types of cancer. It is worth noting that we revealed, for the first time,the content of genomic m~6dA in pancreatic cancer, stromal tumor and colorectal cancer. The significant changes of these DNA epigenetic modifications indicate they may serve as indicators of cancers. In addition, this study will benefit for better understanding of the regulatory roles of these DNA epigenetic modifications in cancers.展开更多
Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper pos...Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper positions.Recently,DCX has been implicated in various cancer processes,suggesting it may influence tumor progression and the tumor microenvironment.Emerging evidence indicates that DCX can modulate cell migration,invasion,and interaction with immune cells,making it a potential player in oncogenesis.However,the role of DCX across different cancer types and its potential as a prognostic biomarker remain underexplored,necessitating a comprehensive analysis.Methods:We utilized The Cancer Genome Atlas to extract data on DCX expression in tumor and adjacent normal tissues across diverse cancer types.Differential expression analysis was conducted using differential expression sequencing 2.Survival analysis was performed with Kaplan-Meier estimates and Cox proportional hazards models.Correlations between DCX expression and tumor mutational burden,microsatellite instability,and immune infiltration were examined using Spearman’s correlation.Results:DCX showed variable expression across cancer types,with significant overexpression in certain tumors such as liver and lung cancer and downexpression in others like breast cancer.High DCX expression was correlated with poor prognosis in adrenocortical carcinoma but with better outcomes in low-grade glioma.Additionally,DCX expression was significantly associated with various immune markers and chemokines,suggesting a role in modulating the immune microenvironment.Conclusion:Our findings highlight the complex role of DCX in cancer,underlining its potential as a prognostic marker and its involvement in immune-related pathways.Targeting DCX could represent a novel approach to modulating tumor behavior and enhancing immune response in cancer therapy.展开更多
Apolipoprotein E(APOE),a gene identified as one of the strongest genetic factors contributing to the risk determinant of developing late-onset Alzheimer’s disease(AD),may also contribute to the risk of cancer.However,...Apolipoprotein E(APOE),a gene identified as one of the strongest genetic factors contributing to the risk determinant of developing late-onset Alzheimer’s disease(AD),may also contribute to the risk of cancer.However,no pan-cancer analysis has been conducted specifically for the APOE gene.In this study,we investigated the oncogenic role of the APOE gene across cancers by GEO(Gene Expression Omnibus)and TCGA(The Cancer Genome Atlas).Based on the available data,we found that most cancer types overexpress APOE,and clear associations exist between the expression level of APOE and prognosis in tumor patients.The expression of APOE also correlates with certain gender-associated tumors including,ovarian cancer,uterine carcinosarcoma,and breast cancer.However,there is a significant negative association between cancer-associatedfibroblast infiltration levels and the expression level of APOE in testicular germ cell tumors.Moreover,acute inflammatory response and protein-activation cascade-associated functions play an important role in the functional mechanisms of APOE.The present pan-cancer analysis of APOE shows that the protein phosphorylation,DNA methylation,and genetic alterations of APOE have a significant clinical relevance for survival prognosis and immune cell infiltration.This novel pan-cancer study outlines the current understanding of APOE oncogenic roles across thirty-three cancers and highlights the complex association between AD and cancers.展开更多
B and T-lymphocyte attenuator(BTLA)plays an immunosuppressive role by inhibiting T-and B-cell functions.BTLA is associated with a variety of diseases,especially cancer immunity.However,the function of BTLA in various ...B and T-lymphocyte attenuator(BTLA)plays an immunosuppressive role by inhibiting T-and B-cell functions.BTLA is associated with a variety of diseases,especially cancer immunity.However,the function of BTLA in various cancers and its clinical prognostic value have still not been comprehensively analyzed.This study aimed to identify the relationship between BTLA and cancer from the perspectives of differences in BTLA expression,its clinical value,immune infiltration,and the correlation with immune-related genes in various cancers.Data regarding mRNA expression,miRNA expression,lncRNA expression,and clinical data of patients of 33 existing cancers were collected from the TCGA database.Target miRNA of BTLA and the lncRNA that interacts with the target miRNA were obtained from the StarBase database.Based on bioinformatics analysis methods,the relationship between various types of cancers and BTLA was thoroughly investigated,and a competing endogenous RNA network of BTLA,target miRNA,and interacting lncRNA was constructed.The Kaplan-Meier(KM)prognostic analysis of BTLA and target miRNA(has-miR-137)in various types of cancers was completed using the KM plotter.BTLA expression varied in different cancers,with statistical significance in nine cancer types.KM plotter to analyze the overall survival(OS)and regression-free survival prognosis of cancer patients revealed that the BTLA expression was statistically different in the OS of 11 types of cancers out of 21 types of cancers;the OS of 8 type of cancers was also statistically different.Correlation analysis of tumor immune genes revealed a positive correlation of BTLA expression with immunosuppressive gene(CTLA4 and PDCD1)expression.Gene Set Enrichment Analysis showed that BTLA and its co-expressed genes mainly act through biological processes and pathways,including immune response regulation,cell surface receptor signaling pathway,antigen binding,antigen receptor-mediated signaling pathway,and leukocyte migration.BTLA has the potential as a prognostic marker for CLL,COAD,NSCLC,and OV and a diagnostic marker for CLL,COAD,and KIRC.BTLA has a close and complex relationship with the occurrence and development of tumors,and cancer immunotherapy for BTLA is worthy of further analysis.展开更多
Sterol o-acyltransferase1(SOAT1)is an enzyme that regulates lipid metabolism.Nevertheless,the predictive value of SOAT1 regarding immune responses in cancer is not fully understood.Herein,we aimed to expound the predi...Sterol o-acyltransferase1(SOAT1)is an enzyme that regulates lipid metabolism.Nevertheless,the predictive value of SOAT1 regarding immune responses in cancer is not fully understood.Herein,we aimed to expound the predictive value and the potential biological functions of SOAT1 in pan-cancer.Raw data related to SOAT1 expression in 33 different types of cancer were acquired from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.SOAT1 expression was significantly increased in most cancers and showed a distinct correlation with prognosis.This enhanced expression of the SOAT1 gene was confirmed by evaluating SOAT1 protein expression using tissue microarrays.In addition,we found significant positive associations between SOAT1 expression levels and infiltrating immune cells,including T cells,neutrophils,and macrophages.Moreover,the co-expression analysis between SOAT1 and immune genes showed that many immune-related genes were increased with enhanced SOAT1 expression.A gene set enrichment analysis(GSEA)revealed that the expression of SOAT1 correlated with the tumor microenvironment,adaptive immune response,interferon signaling,and cytokine signaling.These findings indicate that SOAT1 is a potential candidate marker for predicting prognosis and a promising target for tumor immunotherapy in cancers.展开更多
The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer ...The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer analysis,enhancing understanding of this gene's role in cancer.We observed differential ALYREF expression between tumor and normal samples,correl ating strongly with prognosis in various cancers,particularly kidney renal papillary cell carcinoma(KIRP)and liver hepatocellular carcinoma(LIHC).ALYREF showed a negative correlation with most tumor-infitrating cells in lung squamous cell carcinoma(LUSC)and lymphoid neoplasm difuse large B-cell lymphoma(DLBC),while positive correlations were noted in IIHC,kidney chromophobe(KICH),mesothelioma(MESO),KIRP,pheochromocytoma and paraganglioma(PARD),and glioma(GBMLGG).Aditionally,ALYREF expression was closely associated with tumor heterogeneity,stemness indices,and a high mutation rate in TP53 across these cancers.In conclusion,ALYREF may serve as an oncogenic biomarker in numerous cancers,meriting further research attention.展开更多
Background:Positive regulatory domain-containing 16(PRDM16)plays a key role in brown adipose transcription,but its function in cancer is unclear.Our research to investigate the potential roles of PRDM16 across multipl...Background:Positive regulatory domain-containing 16(PRDM16)plays a key role in brown adipose transcription,but its function in cancer is unclear.Our research to investigate the potential roles of PRDM16 across multiple types of cancer by pan cancer analyses.Methods:UALCAN and TIMER2 database were utilized to evaluate PRDM16 expression in cancer patients.Gene Expression Profiling Interactive Analysis was employed to analyze the overall survival and disease-free survival across all The Cancer Genome Atlas Program tumors.Using the cBioPortal tool,we analyzed the mutation features of PRDM16 for the The Cancer Genome Atlas Program tumors,then utilized the Encyclopedia of RNA Interactomes database to predict the miRNA-mRNA relationships associated with the PRDM16 for all tumors.Results:The expression level of PRDM16 in the tumor tissues is lower than that in the normal tissues.Interesting,the high expression of PRDM16 has a positive effect on the prognosis of kidney clear cell carcinoma and lung adenocarcinoma,but not conducive to the prognosis of most cancers.In multiple cancer types,the expression of PRDM16 was significantly positively correlated with immune infiltration of cancer-associated fibroblasts.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis indicated that PRDM16 may be related to transcriptional misregulation pathway in cancer.We identified potential miRNAs that play regulatory roles of PRDM16 in kidney clear cell carcinoma and lung adenocarcinoma.Conclusion:PRDM16 is expressed in different cancers,it can be used as a biomarker for prognosis of pan-cancer and is associated with immune infiltration.展开更多
Objective Glutamine fructose-6-phosphate transaminase 2(GFPT2)is involved in a wide range of biological functions in human cancer.However,few studies have comprehensively analyzed the correlation between GFPT2 and dif...Objective Glutamine fructose-6-phosphate transaminase 2(GFPT2)is involved in a wide range of biological functions in human cancer.However,few studies have comprehensively analyzed the correlation between GFPT2 and different cancer prognoses and tumor microenvironments(TMEs).Methods We evaluated the expression level and prognostic value of GFPT2 using updated public databases and multiple comprehensive bioinformatics analysis methods and explored the relationship between GFPT2 expression and immune infiltration,immune neoantigens,tumor mutational burden(TMB),and microsatellite instability in pan-cancer.Results GFPT2 was highly expressed in five cancers.GFPT2 expression correlates with the prognosis of several cancers from The Cancer Genome Atlas(TCGA)and is significantly associated with stromal and immune scores in pan-cancer.High GFPT2 expression in BLCA,BRCA,and CHOL was positively correlated with the infiltration of immune cells,such as B-cells,CD4+T,CD8+T cells,dendritic cells,neutrophils,and macrophages.Conclusion High GFPT2 expression may modify the outcomes of patients with BLCA,BRCA,or CHOL cancers by increasing immune cell infiltration.These findings may provide insights for further investigation into GFPT2 as a potential target in pan-cancer.展开更多
Background:Heat shock protein B8(HSPB8)is implicated in autophagy,and its aberrant expression has been linked to both the ini-tiation and progression of tumors.However,the role and function of HSPB8 in colorectal canc...Background:Heat shock protein B8(HSPB8)is implicated in autophagy,and its aberrant expression has been linked to both the ini-tiation and progression of tumors.However,the role and function of HSPB8 in colorectal cancer(CRC)and across multiple cancer types remain unclear.This study aimed to map the transcriptome of autophagy-related genes in CRC and to conduct a pan-cancer analysis of HSPB8 as both a prognostic and immunological biomarker.Methods:We performed bioinformatics analyses on GSE113513 and GSE74602 to identify differentially expressed genes(DEGs)in CRC.These DEGs were then compared with autophagy-related genes to identify critical overlapping genes.The Kaplan-Meier plotter was used to verify the ex-pression of autophagy-linked DEGs and evaluate its prognostic value.The protein expression of Hub gene in CRC was analyzed using the Human Protein Atlas database.The cBioPortal was used to analyze the type and frequency of Hub gene mutations.The TIMER(Tumor Immune Estimation Resource)database was used to study the correlation between HSPB8 and immune infiltration in CRC.Results:In total,825 DEGs were identified,including 8 autophagy-linked DEGs:ATIC,MYC,HSPB8,TNFSF10,BCL2,TP53INP2,ITPR1,and NKX2-3.Survival analysis showed that increased HSPB8 expression significantly correlates with poor prognosis in patients with CRC(p<0.05).HSPB8 was also found to be differentially expressed in various cancer types,correlating with both prognosis and immune infiltration.Further,changes in HSPB8 methylation and phosphorylation status were observed across several cancers,suggesting potential regulatory mechanisms.Therefore,HSPB8 may serve as a crucial prognostic and immunological biomarker in CRC and other cancers.Conclusions:This study provides new insights into the role of autophagy-related genes in cancer progression and highlights HSPB8 as a potential target for cancer diagnostics and therapy.展开更多
Advances in multi-omics datasets and analytical methods have revolutionized cancer research,offering a comprehensive,pan-cancer perspective.Pancancer studies identify shared mechanisms and unique traits across differe...Advances in multi-omics datasets and analytical methods have revolutionized cancer research,offering a comprehensive,pan-cancer perspective.Pancancer studies identify shared mechanisms and unique traits across different cancer types,which are reshaping diagnostic and treatment strategies.However,continued innovation is required to refine these approaches and deepen our understanding of cancer biology and medicine.This review summarized key findings from pan-cancer research and explored their potential to drive future advancements in oncology。展开更多
Deoxyribonuclease 2(DNASE2)is associated with tumor pro-liferation and apoptosis,innate immune signaling,chronic inflammation,and systemic autoinflammatory diseases.However,the role and mechanism of DNASE2’s action i...Deoxyribonuclease 2(DNASE2)is associated with tumor pro-liferation and apoptosis,innate immune signaling,chronic inflammation,and systemic autoinflammatory diseases.However,the role and mechanism of DNASE2’s action in gli-omas remain unclear.In this study,the difference analysis showed that after supplementing normal tissue samples from the Genotype-Tissue Expression(GTEx)dataset,DNASE2 mRNA levels in 30 tumors from The Cancer Genome Atlas(TCGA)showed significant differences,correlated with a poor prognosis in patients with glioblastoma multiforme(GBM).展开更多
The authors regret to note that the affiliations in the above paper were incorrect.The correct author affiliations should be:Lijin Chen a,b,1,Yingying Li b,1,Hong Zhao c,1,Jinyuan Huangb,Huimeng Yan b,Xiaoyan Lin b,∗∗...The authors regret to note that the affiliations in the above paper were incorrect.The correct author affiliations should be:Lijin Chen a,b,1,Yingying Li b,1,Hong Zhao c,1,Jinyuan Huangb,Huimeng Yan b,Xiaoyan Lin b,∗∗,Bin Zhao a,∗a Quanzhou First Hospital Affiliated to Fujian Medical University,Quanzhou,Fujian 362000,China.展开更多
Background:Cancer cells reprogram metabolism for proliferation.Phosphoglycerate kinase 1(PGK1),as a glycolytic enzyme and newly identified protein kinase,coordinates glycolysis and mitochondrial metabolism.However,the...Background:Cancer cells reprogram metabolism for proliferation.Phosphoglycerate kinase 1(PGK1),as a glycolytic enzyme and newly identified protein kinase,coordinates glycolysis and mitochondrial metabolism.However,the clini-cal significance of PGK1 expression and function in cancer progression is unclear.Here,we investigated the relation-ship between the progression and prognosis of multiple cancer types and PGK1 expression and its function in the mitochondrial metabolism regulation.Methods:We performed pan-cancer analyses of PGK1 mRNA level and DNA methylation in 11,908 tumor tissues and 1582 paired normal tissues across 34 cancer types in The Cancer Genome Atlas datasets.Using specific antibodies against PGK1 S203 and PDHK1 T338 phosphorylation,we performed immunohistochemistry with tissue microarray assay in additional 818 cancer cases with 619 paired normal tissues from five cancer types.Results:The PGK1 mRNA level was significantly elevated with hypomethylation in promotor regions and associated with advanced TNM stage in 15 and four cancer types,respectively.In breast carcinoma,elevated PGK1 mRNA level and promoter hypomethylation were associated with poor prognosis.Positively correlated PGK1 S203 and PDHK1 T338 phosphorylation levels were significantly associated with short overall survival(OS)in cancers of the breast,liver,lung,stomach,and esophagus and with advanced TNM stage in breast and esophageal cancers.PGK1 pS203 and PDHK1 pT338 were also independent predictors of short OS in liver,lung,and stomach cancer.Conclusions:The elevated expression,promoter hypomethylation,and phosphorylation of PGK1 and PDHK1 were related with disease progression and short OS in diverse types of cancer.PGK1 and PDHK1 phosphorylation may be potential prognostic biomarkers.展开更多
The DEAD-box RNA helicase(DDX)family plays a critical role in the growth and development of multiple organisms.DDX1 is involved in mRNA/rRNA processing and mature,virus replication and transcription,hormone metabolism...The DEAD-box RNA helicase(DDX)family plays a critical role in the growth and development of multiple organisms.DDX1 is involved in mRNA/rRNA processing and mature,virus replication and transcription,hormone metabolism,tumo-rigenesis,and tumor development.However,how DDX1 functions in various cancers remains unclear.Here,we explored the potential oncogenic roles of DDX1 across 33 tumors with The Cancer Genome Atlas(TCGA)and the Genotype-Tissue Expression(GTEx)databases.DDX1 is highly expressed in breast cancer(BRCA),cholangiocarcinoma(CHOL),and colon adenocarcinoma(COAD),but it is lowly expressed in renal cancers,including kidney renal clear cell carcinoma(KIRC),kidney chromophobe(KICH),and kidney renal papillary cell carcinoma(KIRP).Low expression of DDX1 in KIRC is cor-related with a good prognosis of overall survival(OS)and disease-free survival(DFS).Highly expressed DDX1 is linked to a poor prognosis of OS for adrenocortical carcinoma(ACC),bladder urothelial carcinoma(BLCA),KICH,and liver hepatocellular carcinoma(LIHC).Also,the residue Ser481 of DDX1 had an enhanced phosphorylation level in BRCA and ovarian cancer(OV)but decreased in KIRC.Immune infiltration analysis exhibited that DDX1 expression affected CD8+T cells,and it was significantly associated with MSI(microsatellite instability),TMB(tumor mutational burden),and ICT(immune checkpoint blockade therapy)in tumors.In addition,the depletion of DDX1 dramatically affected the cell viability of human tumor-derived cell lines.DDX1 could affect the DNA repair pathway and the RNA transport/DNA replication processes during tumorigenesis by analyzing the CancerSEA database.Thus,our pan-cancer analysis revealed that DDX1 had complicated impacts on different cancers and might act as a prognostic marker for cancers such as renal cancer.展开更多
基金supported by grants from the Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:Receptor-interacting protein kinases(RIPKs)regulate cell death,inflammation,and immune responses,yet their roles in cancer are not fully understood.This study investigates the expression,genomic alterations,and functional implications of RIPK family members across various cancers.Methods:We collected multi-omics data from The Cancer Genome Atlas and other public databases,including gene expression,copy number variation(CNV),mutation,methylation,tumor mutation burden(TMB),and microsatellite instability(MSI).Differential expression and survival analyses were performed using DESeq2 and Cox proportional hazards models.CNV and mutation data were analyzed with GISTIC2 and Mutect2,and methylation data with the ChAMP package.Correlations with TMB and MSI were assessed using Pearson coefficients,and gene set enrichment analysis was conducted with the MSigDB Hallmark gene sets.Results:RIPK family members show significant differential expression in various cancers,with RIPK1 and RIPK4 frequently altered.Survival analysis reveals heterogeneous impacts on overall survival.CNV and mutation analyses identify high alteration frequencies for RIPK2 and RIPK7,affecting gene expression.RIPK1 and RIPK7 are hypermethylated in several cancers,inversely correlating with RIPK3 expression.RIPK1,RIPK2,RIPK5,RIPK6,and RIPK7 correlate positively with TMB,while RIPK3 shows negative correlations in some cancers.MSI analysis indicates associations with DNA mismatch repair.G ene set enrichment analysis highlights immune-related pathway enrichment for RIPK1,RIPK2,RIPK3,and RIPK6,and cell proliferation and DNA repair pathways for RIPK4 and RIPK5.RIPK family members showed heterogeneous alterations across cancers:for example,RIPK7 was mutated in up to~15%of u terine c orpus e ndometrial c arcinoma and l ung s quamous c ell c arcinoma cases,and RIPK1 and RIPK7 exhibited frequent promoter hypermethylation in multiple tumor types.Several genes displayed context-dependent associations with overall survival and with TMB/MSI.Conclusion:This pan-cancer analysis of the RIPK family reveals their diverse roles and potential as biomarkers and therapeutic targets.The findings emphasize the importance of RIPK genes in tumorigenesis and suggest context-dependent functions across cancer types.Further studies are needed to explore their mechanisms in cancer development and clinical applications.
基金supported by the Shandong Province Medical and Health Technology Project(202303111442).
文摘Background:Long non-coding RNAs(lncRNAs)act as epigenetic regulators for tumor hallmarks.This investigation sought to probe the carcinogenic trait of PAN3-AS1 across pan-cancer comprehensively.Methods:We studied the diagnostic and prognostic features and the immune landscape of PAN3-AS1 across pan-cancer by bioinformatics approaches.The hierarchical regulatory networks governing PAN3-AS1 expression in colon cancer were explored via chromatin immunoprecipitation,luciferase activity assays,and RNA immunoprecipitation,etc.We screened drugs sensitive to WAP four-disulfide core domain 13(WFDC13)by virtual screening and molecular docking.Results:Single-cell transcriptomics demonstrated that a variety of immune populations abnormally expressed PAN3-AS1 beyond tumor cells.Integration of data from multiple databases revealed that PAN3-AS1 was highly expressed and associated with a bad prognosis in various malignancies.Notably,PAN3-AS1 expression was correlated with a suppressive immune microenvironment.Moreover,we observed poor immunotherapy efficacy when PAN3-AS1 was highly expressed in melanoma.In vitro assays and functional enrichment analysis revealed that PAN3-AS1 was associated with cell proliferation and the immune response in colon cancer.Our experiments confirmed that PAN3-AS1 facilitated WFDC13 expression through competitive binding to hsa-miR-423-5p in colon cancer.Moreover,the present paper illustrated that enhancer activity exerts an important modulatory ability for PAN3-AS1 expression.Conclusion:In short,PAN3-AS1 is a valuable biomarker for diagnosis and prognosis.PAN3-AS1 exhibits linkage to a cold tumor immune microenvironment(TME)and forecasts durable benefit from immunotherapy.Addressing the PAN3-AS1/miR-423-5p/WFDC13 axis might provide a novel option for improving immunotherapy efficacy in colon cancer.
基金Supported by the Science and Technology Program of Gansu Province,No.23JRRA1015the International Science and Technology Cooperation Project of Gansu Provincial Science and Technology Department,No.2023YFWA0009the Innovation and Entrepreneurship Project for Young Talents of Lanzhou Science and Technology Bureau,No.2023-4-18.
文摘BACKGROUND Ectonucleoside triphosphate diphosphohydrolase 6(ENTPD6),a member of the ENTPD family,has been implicated in certain cancers,yet a comprehensive analysis across multiple cancer types remains lacking.AIM To systematically evaluate ENTPD6’s expression,prognostic significance,and functions across multiple cancer types.METHODS In this study,we performed a pan-cancer analysis to investigate the correlation between ENTPD6 expression and various factors,including prognosis,genetic alterations,epigenetic modification,immune infiltration,immunotherapy responses,functional enrichment,and drug sensitivity.A tissue microarray of gastrointestinal tumors was used to validate differential ENTPD6 protein expression.RESULTS Pan-cancer analysis revealed that ENTPD6 expression was significantly elevated in many cancers.Immunohistochemistry staining analysis revealed that ENTPD6 expression was significantly higher in esophageal carcinoma,stomach adenocarcinoma,colon adenocarcinoma,rectal adenocarcinoma,and pancreatic adenocarcinoma compared to normal tissues.Furthermore,ENTPD6 expression was strongly associated with immune-infiltrating cells,particularly clusters of differentiation 8+T cells and natural killer cells,and correlated with immune-related genomic features including tumor mutational burden and microsatellite instability.Pathway analysis indicated that ENTPD6 expression was primarily linked to purine and pyrimidine metabolism pathways.Drug sensitivity analysis revealed that high ENTPD6 expression was sensitive to RDEA119,selumetinib,and PD-0325901.CONCLUSION This pan-cancer study elucidates the pivotal role of ENTPD6 in tumor progression and establishes its potential as a therapeutic target for immunotherapeutic approaches in specific malignancies.
基金supported by grants from the Weifang Municipal Health Commission Research Programme Project(No.WFWSJK-2023-032)the Weifang Science and Technology Development Project(No.2023YX053)the Weifang Young Medical Talent Support Program Funding。
文摘Background:NDC80 is pivotal in cell division,particularly in regulating the G2/M transition and mitotic progression.Recent studies have demonstrated that NDC80 is significantly overexpressed in multiple solid tumors.Further analysis has suggested that its high expression is significantly associated with an elevated pathological grade,increased metastatic risk,and shortened overall survival in patients with cancer.However,its precise role in pan-cancer development,progression,and prognosis remains unclear.Methods:We conducted a multi-omics analysis of NDC80 using genomic,transcriptomic,and proteomic data from 33 cancer types in The Cancer Genome Atlas,Clinical Proteomic Tumor Analysis Consortium,Genotype-Tissue Expression,and Human Protein Atlas.Results:The results demonstrated frequent NDC80 mutations across multiple malignancies and significantly elevated expression in tumor tissues compared with that in their normal counterparts,correlating with worse overall and disease-free survival.Moreover,NDC80 expression was strongly associated with oncogenic pathways,key protein regulators,cellular components,myeloid-derived suppressor cell infiltration,ESTIMATE scores,and cancer-related signaling networks.Conclusions:These findings underscore the potential of NDC80 as a prognostic biomarker and therapeutic target for cancer treatment.
基金supported by a grant from the Hefei Municipal Health Commission Applied Medical Research Project(No.Hwk2023zd007)。
文摘Background:Rho GDP dissociation inhibitor 2(ARHGDIB),a key regulator of Rho GTPase,plays a significant role in the onset and progression of cancer by participating in various biological processes.However,the diverse biological roles of ARHGDIB across pan-cancer remain systematically and comprehensively unexplored.We aimed to elucidate the diagnostic and prognostic roles of ARHGDIB and its potential tumor-related mechanisms in human cancers,using bioinformatics approaches.Methods:Data on 33 tumor types were downloaded from The Cancer Genome Atlas,and R software was used to statistically analyze ARHGDIB expression levels and prognostic significance across pan-cancer.Western blot was used to verify the protein expression of ARHGDIB in breast cancer and liver cancer cell lines.Additionally,various databases,including UALCAN,GEPIA,cBioPortal,TIMER,CancerSEA,GSCALite,and GSEA,were used to examine ARHGDIB protein expression across pan-cancer,its correlation with tumor pathological staging,ARHGDIB mutation types and frequencies,and immune cell infiltration.Furthermore,functional analyses at the single-cell level,drug sensitivity assessments,and explorations of related signaling pathways were performed.Results:ARHGDIB exhibits abnormal expression at mRNA and protein levels across various cancers.Western blot results show that ARHGDIB is highly expressed in breast cancer and liver cancer cells.ARHGDIB influences the prognosis of lower-grade glioma,bladder cancer,sarcoma,and skin cutaneous melanoma.It exhibits the highest frequency of gene alterations in uterine carcinosarcoma,primarily characterized by gene amplification.Additionally,ARHGDIB is strongly associated with immune-infiltrating cells and immune checkpoints in the tumor microenvironment.It potentially influences cancer progression through multiple signaling pathways.Conclusions:ARHGDIB is a potential prognostic marker in various cancers and a crucial regulator of the tumor microenvironment.It represents a promising therapeutic target by modulating cancer progression through multiple biological behaviors and signaling pathways.
基金supported by grants from the Tianjin Health Technology Project(Grant No.2022QN106).
文摘Background:The nuclear receptor coactivator(NCOA)family,including NCOA1,NCOA2,and NCOA3,is critical in regulating gene expression through interactions with nuclear receptors and other transcription factors.These coactivators are implicated in various cancers,but their comprehensive roles across different cancer types remain poorly understood.Methods:We performed a pan-cancer bioinformatics analysis using data from The Cancer Genome Atlas and the Genotype-Tissue Expression project.We assessed the differential expression,copy number variations,mutations,methylation status,tumor mutation burden,microsatellite instability,and immune cell infiltration associated with NCOA family members across various cancers.Differential expression analysis was conducted using the DESeq2 package.Methylation data were analyzed using the ChAMP package,and immune cell infiltration was estimated using the CIBERSORT algorithm.Results:NCOA1 and NCOA2 were predominantly downregulated in multiple cancers,suggesting potential tumor suppressor roles,whereas NCOA3 was largely upregulated,indicating a consistent oncogenic function.These expression patterns significantly correlated with patient prognosis.Frequent copy number variations,particularly gains,and high mutation rates were observed in NCOA2.NCOA3 demonstrated consistent hypomethylation in tumors,which was associated with increased gene expression.Significant correlations were found between NCOA expression and tumor mutation burden,microsatellite instability,and immune cell infiltration,indicating their involvement in genomic instability and immune modulation.Conclusion:This comprehensive analysis reveals significant alterations in the expression,genomic,and epigenetic profiles of NCOA family members across various cancers.The findings highlight the multifaceted roles of NCOA1,NCOA2,and NCOA3 in tumorigenesis and their potential as biomarkers and therapeutic targets.Future research should focus on elucidating the mechanisms underlying the associations between NCOA expression,genomic alterations,and immune modulation to develop targeted cancer therapies.
基金financially supported by National Natural Science Foundation of China (No. 22176167)the Key R&D Program of Zhejiang Province (No. 2021C03125)Natural Science Foundation of Zhejiang Province (No. LY19B050007)。
文摘Accumulating evidence in recent years indicates that DNA methylation(5-methyl-2-deoxycytidine,5-mdC) and hydroxymethylation(5-hydroxymethyl-2-deoxycytidine, 5-hmd C) have been implicated in various biological processes, and the aberrations of these DNA cytosine modifications is tightly associated with cancer. N6-methyl-2-deoxyadenosine(m~6dA), as a newly discovered epigenetic modification in genome of mammals, has been demonstrated to play vital regulatory roles in tumorigenesis. However, the content information of m~6dA in human tumor tissues is still limited and pan-cancer analysis of these DNA epigenetic modifications is lacked. Herein, we developed a sensitive and robust stable isotopediluted hydrophilic interaction liquid chromatography-tandem mass spectrometry(HILIC-MS/MS) method for accurate quantification of m~6dA, 5-mdC and 5-hmdC in genomic DNA from 82 pairs of human tumor tissues and matched tumor-adjacent normal tissues. The types of tumors included esophagus cancer, lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, stromal tumor and colorectal cancer.Compared to the normal tissues, we revealed the level of m6dA was increased in tumor tissues of esophagus cancer, lung cancer and liver cancer, whereas the level of m~6dA was diminished in tumor tissues of pancreatic cancer and gastric cancer;while the contents of 5-mdC and 5-hmdC exhibited significant decrease in tumor tissues of most types of cancer. It is worth noting that we revealed, for the first time,the content of genomic m~6dA in pancreatic cancer, stromal tumor and colorectal cancer. The significant changes of these DNA epigenetic modifications indicate they may serve as indicators of cancers. In addition, this study will benefit for better understanding of the regulatory roles of these DNA epigenetic modifications in cancers.
基金Tianjin Health Technology Project(Grant no.2022QN106).
文摘Background:Doublecortin(DCX),a microtubule-associated protein,is best known for its critical role in neuronal migration during neural development,where it stabilizes microtubules and guides neurons to their proper positions.Recently,DCX has been implicated in various cancer processes,suggesting it may influence tumor progression and the tumor microenvironment.Emerging evidence indicates that DCX can modulate cell migration,invasion,and interaction with immune cells,making it a potential player in oncogenesis.However,the role of DCX across different cancer types and its potential as a prognostic biomarker remain underexplored,necessitating a comprehensive analysis.Methods:We utilized The Cancer Genome Atlas to extract data on DCX expression in tumor and adjacent normal tissues across diverse cancer types.Differential expression analysis was conducted using differential expression sequencing 2.Survival analysis was performed with Kaplan-Meier estimates and Cox proportional hazards models.Correlations between DCX expression and tumor mutational burden,microsatellite instability,and immune infiltration were examined using Spearman’s correlation.Results:DCX showed variable expression across cancer types,with significant overexpression in certain tumors such as liver and lung cancer and downexpression in others like breast cancer.High DCX expression was correlated with poor prognosis in adrenocortical carcinoma but with better outcomes in low-grade glioma.Additionally,DCX expression was significantly associated with various immune markers and chemokines,suggesting a role in modulating the immune microenvironment.Conclusion:Our findings highlight the complex role of DCX in cancer,underlining its potential as a prognostic marker and its involvement in immune-related pathways.Targeting DCX could represent a novel approach to modulating tumor behavior and enhancing immune response in cancer therapy.
基金supported by the Pujiang Talent Program from Shanghai Municipal Human Resource Bureau and Shanghai Science and Technology Committee to Shoukai Yu.The Grant No.is 19PJC085.
文摘Apolipoprotein E(APOE),a gene identified as one of the strongest genetic factors contributing to the risk determinant of developing late-onset Alzheimer’s disease(AD),may also contribute to the risk of cancer.However,no pan-cancer analysis has been conducted specifically for the APOE gene.In this study,we investigated the oncogenic role of the APOE gene across cancers by GEO(Gene Expression Omnibus)and TCGA(The Cancer Genome Atlas).Based on the available data,we found that most cancer types overexpress APOE,and clear associations exist between the expression level of APOE and prognosis in tumor patients.The expression of APOE also correlates with certain gender-associated tumors including,ovarian cancer,uterine carcinosarcoma,and breast cancer.However,there is a significant negative association between cancer-associatedfibroblast infiltration levels and the expression level of APOE in testicular germ cell tumors.Moreover,acute inflammatory response and protein-activation cascade-associated functions play an important role in the functional mechanisms of APOE.The present pan-cancer analysis of APOE shows that the protein phosphorylation,DNA methylation,and genetic alterations of APOE have a significant clinical relevance for survival prognosis and immune cell infiltration.This novel pan-cancer study outlines the current understanding of APOE oncogenic roles across thirty-three cancers and highlights the complex association between AD and cancers.
基金funded by the Central to guide local scientific and Technological Development(ZYYDDFFZZJ-1)Natural Science Foundation of Gansu Province,China(No.18JR3RA052)+2 种基金Lanzhou Talent Innovation and Entrepreneurship Project Task Contract(No.2016-RC-56)Gansu Da Vinci Robot High-End Diagnosis and Treatment Team Construction Project,and Gansu Provincial Youth Science and Technology Fund Program(20JR10RA415)National Key Research and Development Program(No.2018YFC1311500).
文摘B and T-lymphocyte attenuator(BTLA)plays an immunosuppressive role by inhibiting T-and B-cell functions.BTLA is associated with a variety of diseases,especially cancer immunity.However,the function of BTLA in various cancers and its clinical prognostic value have still not been comprehensively analyzed.This study aimed to identify the relationship between BTLA and cancer from the perspectives of differences in BTLA expression,its clinical value,immune infiltration,and the correlation with immune-related genes in various cancers.Data regarding mRNA expression,miRNA expression,lncRNA expression,and clinical data of patients of 33 existing cancers were collected from the TCGA database.Target miRNA of BTLA and the lncRNA that interacts with the target miRNA were obtained from the StarBase database.Based on bioinformatics analysis methods,the relationship between various types of cancers and BTLA was thoroughly investigated,and a competing endogenous RNA network of BTLA,target miRNA,and interacting lncRNA was constructed.The Kaplan-Meier(KM)prognostic analysis of BTLA and target miRNA(has-miR-137)in various types of cancers was completed using the KM plotter.BTLA expression varied in different cancers,with statistical significance in nine cancer types.KM plotter to analyze the overall survival(OS)and regression-free survival prognosis of cancer patients revealed that the BTLA expression was statistically different in the OS of 11 types of cancers out of 21 types of cancers;the OS of 8 type of cancers was also statistically different.Correlation analysis of tumor immune genes revealed a positive correlation of BTLA expression with immunosuppressive gene(CTLA4 and PDCD1)expression.Gene Set Enrichment Analysis showed that BTLA and its co-expressed genes mainly act through biological processes and pathways,including immune response regulation,cell surface receptor signaling pathway,antigen binding,antigen receptor-mediated signaling pathway,and leukocyte migration.BTLA has the potential as a prognostic marker for CLL,COAD,NSCLC,and OV and a diagnostic marker for CLL,COAD,and KIRC.BTLA has a close and complex relationship with the occurrence and development of tumors,and cancer immunotherapy for BTLA is worthy of further analysis.
基金This work was mainly supported by the Science and Technology Innovation Fund Project of Shanghai Jinshan District Science and Technology Commission(No.2021-3-55)All sponsors or funders played no roles in the study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Sterol o-acyltransferase1(SOAT1)is an enzyme that regulates lipid metabolism.Nevertheless,the predictive value of SOAT1 regarding immune responses in cancer is not fully understood.Herein,we aimed to expound the predictive value and the potential biological functions of SOAT1 in pan-cancer.Raw data related to SOAT1 expression in 33 different types of cancer were acquired from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases.SOAT1 expression was significantly increased in most cancers and showed a distinct correlation with prognosis.This enhanced expression of the SOAT1 gene was confirmed by evaluating SOAT1 protein expression using tissue microarrays.In addition,we found significant positive associations between SOAT1 expression levels and infiltrating immune cells,including T cells,neutrophils,and macrophages.Moreover,the co-expression analysis between SOAT1 and immune genes showed that many immune-related genes were increased with enhanced SOAT1 expression.A gene set enrichment analysis(GSEA)revealed that the expression of SOAT1 correlated with the tumor microenvironment,adaptive immune response,interferon signaling,and cytokine signaling.These findings indicate that SOAT1 is a potential candidate marker for predicting prognosis and a promising target for tumor immunotherapy in cancers.
基金the Chinese Scholarship Council(Grant No.202206240086)the National Natural Science Foundation of China(Grant No.82170432)programs from Science and Technology Department of Sichuan Province(Grant No.2020YFSY0024).
文摘The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer analysis,enhancing understanding of this gene's role in cancer.We observed differential ALYREF expression between tumor and normal samples,correl ating strongly with prognosis in various cancers,particularly kidney renal papillary cell carcinoma(KIRP)and liver hepatocellular carcinoma(LIHC).ALYREF showed a negative correlation with most tumor-infitrating cells in lung squamous cell carcinoma(LUSC)and lymphoid neoplasm difuse large B-cell lymphoma(DLBC),while positive correlations were noted in IIHC,kidney chromophobe(KICH),mesothelioma(MESO),KIRP,pheochromocytoma and paraganglioma(PARD),and glioma(GBMLGG).Aditionally,ALYREF expression was closely associated with tumor heterogeneity,stemness indices,and a high mutation rate in TP53 across these cancers.In conclusion,ALYREF may serve as an oncogenic biomarker in numerous cancers,meriting further research attention.
基金This study was financially supported by the Young Teachers Support Program of Hubei University of Chinese Medicine(2021ZZX025)Hubei Province College Students’innovation and entrepreneurship training program(S202210507018).
文摘Background:Positive regulatory domain-containing 16(PRDM16)plays a key role in brown adipose transcription,but its function in cancer is unclear.Our research to investigate the potential roles of PRDM16 across multiple types of cancer by pan cancer analyses.Methods:UALCAN and TIMER2 database were utilized to evaluate PRDM16 expression in cancer patients.Gene Expression Profiling Interactive Analysis was employed to analyze the overall survival and disease-free survival across all The Cancer Genome Atlas Program tumors.Using the cBioPortal tool,we analyzed the mutation features of PRDM16 for the The Cancer Genome Atlas Program tumors,then utilized the Encyclopedia of RNA Interactomes database to predict the miRNA-mRNA relationships associated with the PRDM16 for all tumors.Results:The expression level of PRDM16 in the tumor tissues is lower than that in the normal tissues.Interesting,the high expression of PRDM16 has a positive effect on the prognosis of kidney clear cell carcinoma and lung adenocarcinoma,but not conducive to the prognosis of most cancers.In multiple cancer types,the expression of PRDM16 was significantly positively correlated with immune infiltration of cancer-associated fibroblasts.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis indicated that PRDM16 may be related to transcriptional misregulation pathway in cancer.We identified potential miRNAs that play regulatory roles of PRDM16 in kidney clear cell carcinoma and lung adenocarcinoma.Conclusion:PRDM16 is expressed in different cancers,it can be used as a biomarker for prognosis of pan-cancer and is associated with immune infiltration.
基金Supported by a grant from the National Natural Science Foundation of China(No.81700256).
文摘Objective Glutamine fructose-6-phosphate transaminase 2(GFPT2)is involved in a wide range of biological functions in human cancer.However,few studies have comprehensively analyzed the correlation between GFPT2 and different cancer prognoses and tumor microenvironments(TMEs).Methods We evaluated the expression level and prognostic value of GFPT2 using updated public databases and multiple comprehensive bioinformatics analysis methods and explored the relationship between GFPT2 expression and immune infiltration,immune neoantigens,tumor mutational burden(TMB),and microsatellite instability in pan-cancer.Results GFPT2 was highly expressed in five cancers.GFPT2 expression correlates with the prognosis of several cancers from The Cancer Genome Atlas(TCGA)and is significantly associated with stromal and immune scores in pan-cancer.High GFPT2 expression in BLCA,BRCA,and CHOL was positively correlated with the infiltration of immune cells,such as B-cells,CD4+T,CD8+T cells,dendritic cells,neutrophils,and macrophages.Conclusion High GFPT2 expression may modify the outcomes of patients with BLCA,BRCA,or CHOL cancers by increasing immune cell infiltration.These findings may provide insights for further investigation into GFPT2 as a potential target in pan-cancer.
基金supported by the NationalNatural Science Foundation of China(no.32360888)the Jiangxi Students’Platform for Innovation and Entrepreneurship Training Program(no.202411843023).
文摘Background:Heat shock protein B8(HSPB8)is implicated in autophagy,and its aberrant expression has been linked to both the ini-tiation and progression of tumors.However,the role and function of HSPB8 in colorectal cancer(CRC)and across multiple cancer types remain unclear.This study aimed to map the transcriptome of autophagy-related genes in CRC and to conduct a pan-cancer analysis of HSPB8 as both a prognostic and immunological biomarker.Methods:We performed bioinformatics analyses on GSE113513 and GSE74602 to identify differentially expressed genes(DEGs)in CRC.These DEGs were then compared with autophagy-related genes to identify critical overlapping genes.The Kaplan-Meier plotter was used to verify the ex-pression of autophagy-linked DEGs and evaluate its prognostic value.The protein expression of Hub gene in CRC was analyzed using the Human Protein Atlas database.The cBioPortal was used to analyze the type and frequency of Hub gene mutations.The TIMER(Tumor Immune Estimation Resource)database was used to study the correlation between HSPB8 and immune infiltration in CRC.Results:In total,825 DEGs were identified,including 8 autophagy-linked DEGs:ATIC,MYC,HSPB8,TNFSF10,BCL2,TP53INP2,ITPR1,and NKX2-3.Survival analysis showed that increased HSPB8 expression significantly correlates with poor prognosis in patients with CRC(p<0.05).HSPB8 was also found to be differentially expressed in various cancer types,correlating with both prognosis and immune infiltration.Further,changes in HSPB8 methylation and phosphorylation status were observed across several cancers,suggesting potential regulatory mechanisms.Therefore,HSPB8 may serve as a crucial prognostic and immunological biomarker in CRC and other cancers.Conclusions:This study provides new insights into the role of autophagy-related genes in cancer progression and highlights HSPB8 as a potential target for cancer diagnostics and therapy.
基金supported by the Self-supporting Program of Guangzhou Laboratory(SRPG22007)the CAS Research Fund(XDB38050200)+1 种基金the National Key Research and Development Program of China(2021YFA0910100)Healthy Zhejiang One Million People Cohort(K-20230085).
文摘Advances in multi-omics datasets and analytical methods have revolutionized cancer research,offering a comprehensive,pan-cancer perspective.Pancancer studies identify shared mechanisms and unique traits across different cancer types,which are reshaping diagnostic and treatment strategies.However,continued innovation is required to refine these approaches and deepen our understanding of cancer biology and medicine.This review summarized key findings from pan-cancer research and explored their potential to drive future advancements in oncology。
基金funded by the National Natural Science Foundation of China(No.82373403 to Y.C.)the Beijing New-Star Plan of Science and Technology(China)(No.Z201100006820148 to Y.C.).
文摘Deoxyribonuclease 2(DNASE2)is associated with tumor pro-liferation and apoptosis,innate immune signaling,chronic inflammation,and systemic autoinflammatory diseases.However,the role and mechanism of DNASE2’s action in gli-omas remain unclear.In this study,the difference analysis showed that after supplementing normal tissue samples from the Genotype-Tissue Expression(GTEx)dataset,DNASE2 mRNA levels in 30 tumors from The Cancer Genome Atlas(TCGA)showed significant differences,correlated with a poor prognosis in patients with glioblastoma multiforme(GBM).
文摘The authors regret to note that the affiliations in the above paper were incorrect.The correct author affiliations should be:Lijin Chen a,b,1,Yingying Li b,1,Hong Zhao c,1,Jinyuan Huangb,Huimeng Yan b,Xiaoyan Lin b,∗∗,Bin Zhao a,∗a Quanzhou First Hospital Affiliated to Fujian Medical University,Quanzhou,Fujian 362000,China.
基金This study was funded by The National Key R&D Program of China(2017YFC1308702,2017YFC1311000,2018YFC1312100)the Beijing Municipal Science&Technology Commission(Z181100006218032,Z181100001918002)+1 种基金the CAMS Initiative for Innovative Medicine(2017-I2M-1-005,2017-I2M-2-003,2019-I2M-2-002)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2017PT32001,2017PT32017).
文摘Background:Cancer cells reprogram metabolism for proliferation.Phosphoglycerate kinase 1(PGK1),as a glycolytic enzyme and newly identified protein kinase,coordinates glycolysis and mitochondrial metabolism.However,the clini-cal significance of PGK1 expression and function in cancer progression is unclear.Here,we investigated the relation-ship between the progression and prognosis of multiple cancer types and PGK1 expression and its function in the mitochondrial metabolism regulation.Methods:We performed pan-cancer analyses of PGK1 mRNA level and DNA methylation in 11,908 tumor tissues and 1582 paired normal tissues across 34 cancer types in The Cancer Genome Atlas datasets.Using specific antibodies against PGK1 S203 and PDHK1 T338 phosphorylation,we performed immunohistochemistry with tissue microarray assay in additional 818 cancer cases with 619 paired normal tissues from five cancer types.Results:The PGK1 mRNA level was significantly elevated with hypomethylation in promotor regions and associated with advanced TNM stage in 15 and four cancer types,respectively.In breast carcinoma,elevated PGK1 mRNA level and promoter hypomethylation were associated with poor prognosis.Positively correlated PGK1 S203 and PDHK1 T338 phosphorylation levels were significantly associated with short overall survival(OS)in cancers of the breast,liver,lung,stomach,and esophagus and with advanced TNM stage in breast and esophageal cancers.PGK1 pS203 and PDHK1 pT338 were also independent predictors of short OS in liver,lung,and stomach cancer.Conclusions:The elevated expression,promoter hypomethylation,and phosphorylation of PGK1 and PDHK1 were related with disease progression and short OS in diverse types of cancer.PGK1 and PDHK1 phosphorylation may be potential prognostic biomarkers.
基金supported by grants from the National Natural Science Foundation of China(82071782)the Shanghai Committee of Science and Technology(20XD1400800)to JL.
文摘The DEAD-box RNA helicase(DDX)family plays a critical role in the growth and development of multiple organisms.DDX1 is involved in mRNA/rRNA processing and mature,virus replication and transcription,hormone metabolism,tumo-rigenesis,and tumor development.However,how DDX1 functions in various cancers remains unclear.Here,we explored the potential oncogenic roles of DDX1 across 33 tumors with The Cancer Genome Atlas(TCGA)and the Genotype-Tissue Expression(GTEx)databases.DDX1 is highly expressed in breast cancer(BRCA),cholangiocarcinoma(CHOL),and colon adenocarcinoma(COAD),but it is lowly expressed in renal cancers,including kidney renal clear cell carcinoma(KIRC),kidney chromophobe(KICH),and kidney renal papillary cell carcinoma(KIRP).Low expression of DDX1 in KIRC is cor-related with a good prognosis of overall survival(OS)and disease-free survival(DFS).Highly expressed DDX1 is linked to a poor prognosis of OS for adrenocortical carcinoma(ACC),bladder urothelial carcinoma(BLCA),KICH,and liver hepatocellular carcinoma(LIHC).Also,the residue Ser481 of DDX1 had an enhanced phosphorylation level in BRCA and ovarian cancer(OV)but decreased in KIRC.Immune infiltration analysis exhibited that DDX1 expression affected CD8+T cells,and it was significantly associated with MSI(microsatellite instability),TMB(tumor mutational burden),and ICT(immune checkpoint blockade therapy)in tumors.In addition,the depletion of DDX1 dramatically affected the cell viability of human tumor-derived cell lines.DDX1 could affect the DNA repair pathway and the RNA transport/DNA replication processes during tumorigenesis by analyzing the CancerSEA database.Thus,our pan-cancer analysis revealed that DDX1 had complicated impacts on different cancers and might act as a prognostic marker for cancers such as renal cancer.
