Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is s...Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is still limited understanding of the peripheral immune inflammato ry response in spinal cord inju ry.In this study.we obtained microRNA expression profiles from the peripheral blood of patients with spinal co rd injury using high-throughput sequencing.We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus(GEO)database(GSE151371).We identified 54 differentially expressed microRNAs and 1656 diffe rentially expressed genes using bioinformatics approaches.Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways,such as neutrophil extracellular trap formation pathway,T cell receptor signaling pathway,and nuclear factor-κB signal pathway,we re abnormally activated or inhibited in spinal cord inju ry patient samples.We applied an integrated strategy that combines weighted gene co-expression network analysis,LASSO logistic regression,and SVM-RFE algorithm and identified three biomarke rs associated with spinal cord injury:ANO10,BST1,and ZFP36L2.We verified the expression levels and diagnostic perfo rmance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve.Quantitative polymerase chain reaction results showed that ANO20 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients.We also constructed a small RNA-mRNA interaction network using Cytoscape.Additionally,we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal co rd injury patients using the CIBERSORT tool.The proportions of naive B cells,plasma cells,monocytes,and neutrophils were increased while the proportions of memory B cells,CD8^(+)T cells,resting natural killer cells,resting dendritic cells,and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects,and ANO10,BST1 and ZFP26L2we re closely related to the proportion of certain immune cell types.The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal co rd inju ry and suggest that ANO10,BST2,and ZFP36L2 are potential biomarkers for spinal cord injury.The study was registe red in the Chinese Clinical Trial Registry(registration No.ChiCTR2200066985,December 12,2022).展开更多
Background:Pancreatic ductal adenocarcinoma(PDAC)has a rich and complex tumor immune microenvironment(TIME).M2 macrophages are among the most extensively infiltrated immune cells in the TIME and are necessary for the g...Background:Pancreatic ductal adenocarcinoma(PDAC)has a rich and complex tumor immune microenvironment(TIME).M2 macrophages are among the most extensively infiltrated immune cells in the TIME and are necessary for the growth and migration of cancers.However,the mechanisms and targets mediating M2 macrophage infiltration in pancreatic cancer remain elusive.Methods:The M2 macrophage infiltration score of patients was assessed using the xCell algorithm.Using weighted gene co-expression network analysis(WGCNA),module genes associated with M2 macrophages were identified,and a predictive model was designed.The variations in immunological cell patterns,cancer mutations,and enrichment pathways between the cohorts with the high-and low-risk were examined.Additionally,the expression of FCGR3A and RNASE2,as well as their association with M2 macrophages were evaluated using the HPA,TNMplot,and GEPIA2 databases and verified by tissue immunofluorescence staining.Moreover,in vitro cell experiments were conducted,where FCGR3A was knocked down in pancreatic cancer cells using siRNA to analyze its effects on M2 macrophage infiltration,tumor proliferation,and metastasis.Results:The prognosis of patients in high-risk and low-risk groups was successfully distinguished using a prognostic risk score model of M2 macrophage-related genes(p=0.024).Between the high-and low-risk cohorts,there have been notable variations in immune cell infiltration patterns,tumor mutations,and biological functions.The risk score was linked to the manifestation of prevalent immunological checkpoints,immunological scores,and stroma values(all p<0.05).In vitro experiments and tissue immunofluorescence staining revealed that FCGR3A can promote the infiltration or polarization of M2 macrophages and enhance tumor proliferation and migration.Conclusions:In this study,an M2 macrophage-related pancreatic cancer risk score model was established,and found that FCGR3A was correlated with tumor formation,metastasis,and M2 macrophage infiltration.展开更多
目的:探究肿瘤浸润免疫细胞(TIICs)浸润程度与头颈部鳞状细胞癌(HNSCC)患者预后的关系,并基于多种免疫细胞构建预后模型。方法:从TCGA数据库中下载515例HNSCC样本和44例正常对照样本的基因表达谱和生存信息,利用CIBERSORT算法计算每个...目的:探究肿瘤浸润免疫细胞(TIICs)浸润程度与头颈部鳞状细胞癌(HNSCC)患者预后的关系,并基于多种免疫细胞构建预后模型。方法:从TCGA数据库中下载515例HNSCC样本和44例正常对照样本的基因表达谱和生存信息,利用CIBERSORT算法计算每个样本中不同免疫细胞的占比,进行免疫细胞浸润分析和Kaplan-Meier生存分析。通过LASSO回归、单因素和多因素Cox回归筛选HNSCC样本中免疫细胞并构建免疫细胞风险评分预后模型,采用Kaplan-Meier法和ROC曲线评估该模型。结果:在22种TIICs中,M0、M1和M2巨噬细胞具有相对高的百分比,约占40%。CD8+T细胞与活化CD4+记忆T细胞呈显著正相关(r = 0.55),而与M0巨噬细胞(r = −0.53)呈显著负相关。生存分析表明高表达的调节性T细胞(P P P P Objective: This paper aims to investigate the relationship between the degree of tumor infiltrating immune cells (TIICs) and prognosis of head and neck squamous cell carcinoma (HNSCC) patients, and construct a prognostic model based on multiple immune cells. Methods: The gene expression profiles and survival information of 515 HNSCC samples and 44 normal control samples were downloaded from the TCGA database. The proportion of different immune cells in each sample was calculated using the CIBERSORT algorithm, and immune cell infiltration analysis and Kaplan-Meier survival analysis were performed. The immune cells in HNSCC samples were screened by LASSO regression, univariate and multivariate Cox regression, and an immune cell risk scoring prognostic model was constructed. The model was evaluated by Kaplan-Meier method and ROC curve. Results: Among the 22 TIICs, M0, M1, and M2 macrophages had relatively high percentages, accounting for about 40%. CD8+T cells were significantly positively correlated with activated CD4+ memory T cells (r = 0.55), while significantly negatively correlated with M0 macrophages (r = −0.53). Survival analysis showed that high expression of regulatory T cells (P P P P < 0.001). Conclusion: TIICs are closely related to the prognosis of HNSCC patients. Regulatory T cells may be considered as a target for treatment of HNSCC, and the prognostic model constructed in this study may provide reference for clinical prognosis.展开更多
基金supported by the Notional Natural Science Foundation of China,No.81960417 (to JX)Guangxi Key Research and Development Program,No.GuiKeA B20159027 (to JX)the Natural Science Foundation of Guangxi Zhuang Autonomous Region,No.2022GXNSFBA035545 (to YG)。
文摘Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal co rd injury.They can greatly affect nerve regeneration and functional recovery.However,there is still limited understanding of the peripheral immune inflammato ry response in spinal cord inju ry.In this study.we obtained microRNA expression profiles from the peripheral blood of patients with spinal co rd injury using high-throughput sequencing.We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus(GEO)database(GSE151371).We identified 54 differentially expressed microRNAs and 1656 diffe rentially expressed genes using bioinformatics approaches.Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways,such as neutrophil extracellular trap formation pathway,T cell receptor signaling pathway,and nuclear factor-κB signal pathway,we re abnormally activated or inhibited in spinal cord inju ry patient samples.We applied an integrated strategy that combines weighted gene co-expression network analysis,LASSO logistic regression,and SVM-RFE algorithm and identified three biomarke rs associated with spinal cord injury:ANO10,BST1,and ZFP36L2.We verified the expression levels and diagnostic perfo rmance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve.Quantitative polymerase chain reaction results showed that ANO20 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients.We also constructed a small RNA-mRNA interaction network using Cytoscape.Additionally,we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal co rd injury patients using the CIBERSORT tool.The proportions of naive B cells,plasma cells,monocytes,and neutrophils were increased while the proportions of memory B cells,CD8^(+)T cells,resting natural killer cells,resting dendritic cells,and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects,and ANO10,BST1 and ZFP26L2we re closely related to the proportion of certain immune cell types.The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal co rd inju ry and suggest that ANO10,BST2,and ZFP36L2 are potential biomarkers for spinal cord injury.The study was registe red in the Chinese Clinical Trial Registry(registration No.ChiCTR2200066985,December 12,2022).
文摘Background:Pancreatic ductal adenocarcinoma(PDAC)has a rich and complex tumor immune microenvironment(TIME).M2 macrophages are among the most extensively infiltrated immune cells in the TIME and are necessary for the growth and migration of cancers.However,the mechanisms and targets mediating M2 macrophage infiltration in pancreatic cancer remain elusive.Methods:The M2 macrophage infiltration score of patients was assessed using the xCell algorithm.Using weighted gene co-expression network analysis(WGCNA),module genes associated with M2 macrophages were identified,and a predictive model was designed.The variations in immunological cell patterns,cancer mutations,and enrichment pathways between the cohorts with the high-and low-risk were examined.Additionally,the expression of FCGR3A and RNASE2,as well as their association with M2 macrophages were evaluated using the HPA,TNMplot,and GEPIA2 databases and verified by tissue immunofluorescence staining.Moreover,in vitro cell experiments were conducted,where FCGR3A was knocked down in pancreatic cancer cells using siRNA to analyze its effects on M2 macrophage infiltration,tumor proliferation,and metastasis.Results:The prognosis of patients in high-risk and low-risk groups was successfully distinguished using a prognostic risk score model of M2 macrophage-related genes(p=0.024).Between the high-and low-risk cohorts,there have been notable variations in immune cell infiltration patterns,tumor mutations,and biological functions.The risk score was linked to the manifestation of prevalent immunological checkpoints,immunological scores,and stroma values(all p<0.05).In vitro experiments and tissue immunofluorescence staining revealed that FCGR3A can promote the infiltration or polarization of M2 macrophages and enhance tumor proliferation and migration.Conclusions:In this study,an M2 macrophage-related pancreatic cancer risk score model was established,and found that FCGR3A was correlated with tumor formation,metastasis,and M2 macrophage infiltration.
文摘目的:探究肿瘤浸润免疫细胞(TIICs)浸润程度与头颈部鳞状细胞癌(HNSCC)患者预后的关系,并基于多种免疫细胞构建预后模型。方法:从TCGA数据库中下载515例HNSCC样本和44例正常对照样本的基因表达谱和生存信息,利用CIBERSORT算法计算每个样本中不同免疫细胞的占比,进行免疫细胞浸润分析和Kaplan-Meier生存分析。通过LASSO回归、单因素和多因素Cox回归筛选HNSCC样本中免疫细胞并构建免疫细胞风险评分预后模型,采用Kaplan-Meier法和ROC曲线评估该模型。结果:在22种TIICs中,M0、M1和M2巨噬细胞具有相对高的百分比,约占40%。CD8+T细胞与活化CD4+记忆T细胞呈显著正相关(r = 0.55),而与M0巨噬细胞(r = −0.53)呈显著负相关。生存分析表明高表达的调节性T细胞(P P P P Objective: This paper aims to investigate the relationship between the degree of tumor infiltrating immune cells (TIICs) and prognosis of head and neck squamous cell carcinoma (HNSCC) patients, and construct a prognostic model based on multiple immune cells. Methods: The gene expression profiles and survival information of 515 HNSCC samples and 44 normal control samples were downloaded from the TCGA database. The proportion of different immune cells in each sample was calculated using the CIBERSORT algorithm, and immune cell infiltration analysis and Kaplan-Meier survival analysis were performed. The immune cells in HNSCC samples were screened by LASSO regression, univariate and multivariate Cox regression, and an immune cell risk scoring prognostic model was constructed. The model was evaluated by Kaplan-Meier method and ROC curve. Results: Among the 22 TIICs, M0, M1, and M2 macrophages had relatively high percentages, accounting for about 40%. CD8+T cells were significantly positively correlated with activated CD4+ memory T cells (r = 0.55), while significantly negatively correlated with M0 macrophages (r = −0.53). Survival analysis showed that high expression of regulatory T cells (P P P P < 0.001). Conclusion: TIICs are closely related to the prognosis of HNSCC patients. Regulatory T cells may be considered as a target for treatment of HNSCC, and the prognostic model constructed in this study may provide reference for clinical prognosis.
