目的:利用生信分析探讨细胞因子IL-12及IFN-γ对乳腺癌患者免疫微环境的影响,并结合临床病理特征,对其评估新辅助化疗疗效的价值进行研究。方法:在基因表达综合(GEO)数据库中下载GSE163882,比较IL-12相对应基因IL12B及IFN-γ相对应基因I...目的:利用生信分析探讨细胞因子IL-12及IFN-γ对乳腺癌患者免疫微环境的影响,并结合临床病理特征,对其评估新辅助化疗疗效的价值进行研究。方法:在基因表达综合(GEO)数据库中下载GSE163882,比较IL-12相对应基因IL12B及IFN-γ相对应基因IFNG在病理完全缓解(pCR)患者和残留病灶(RD)患者中的表达。收集于我院接受新辅助化疗的50例乳腺癌患者的临床资料,使用卡方检验分析临床病理特征与新辅助化疗疗效的相关性;通过ROC曲线评估血清IL-12、IFN-γ的预测价值,并且确定最佳截断值;采用二元Logistic回归进行多因素分析。通过ssGSEA免疫浸润分析IL12B和IFNG与免疫细胞浸润的相关性;采用GO和KEGG功能富集分析,探讨相关基因潜在生物学功能及信号通路。结果:在GEO数据库GSE163882数据集中IL12B和IFNG在pCR患者中呈现高表达。于我院收治的临床患者中pCR患者化疗前血清IL-12和IFN-γ水平明显高于非pCR组(P γ表达状态显著相关(P γ水平是新辅助化疗疗效的独立影响因素。免疫浸润分析显示,活化CD4 T细胞、活化CD8 T细胞、活化B细胞和自然杀伤细胞在pCR患者中高度浸润。结论:血清IL-12和IFN-γ表达状态与新辅助化疗效果具有相关性,化疗前血清IFN-γ高表达是pCR的独立预测因子。Objective: To investigate the effects of cytokines IL-12 and IFN-γ on the immune microenvironment of breast cancer patients by means of Bioinformatics analysis, and to study their value in evaluating the efficacy of neoadjuvant chemotherapy combined with clinicopathological characteristics. Methods: GSE163882 was downloaded from the Gene Expression Omnibus database, and the expressions of IL-12 corresponding gene IL12B and IFNG corresponding gene IFN-γ were compared in pathologic complete response patients and residual lesion patients. The clinical data of 50 breast cancer patients who received neoadjuvant chemotherapy at The Affiliated Hospital of Qingdao University were collected. Chi-square test was used to analyze the correlation between clinicopathological features and the efficacy of neoadjuvant chemotherapy. The predictive value of serum IL-12 and IFN-γ was evaluated by ROC curve. Multivariate analysis was performed by binary Logistic regression. The correlation between IL12B and IFNG and immune cell infiltration was analyzed by ssGSEA immunoinfiltration. GO and KEGG functional enrichment analysis were used to explore the potential biological functions and signaling pathways of related genes. Results: IL12B and IFNG were highly expressed in pCR patients in the GSE163882 dataset. The serum levels of IL-12 and IFN-γ in pCR patients before chemotherapy were significantly higher than those in non-PCR group (P γ expression after neoadjuvant chemotherapy (P γ level before chemotherapy was an independent factor influencing the efficacy of neoadjuvant chemotherapy. Immunoinfiltration analysis showed that activated CD4 T cells, activated CD8 T cells, activated B cells, and natural killer cells were highly infiltrated in pCR patients. Conclusion: The expression of serum IL-12 and IFN-γ is correlated with the effect of neoadjuvant chemotherapy, and the high expression of serum IFN-γ before chemotherapy is an independent predictor of pCR.展开更多
Objective Histamine N-methyltransferase(HNMT)is involved primarily in histamine metabolism,but emerging evidence suggests its potential role in cancer progression.This study investigated the role of HNMT in nasopharyn...Objective Histamine N-methyltransferase(HNMT)is involved primarily in histamine metabolism,but emerging evidence suggests its potential role in cancer progression.This study investigated the role of HNMT in nasopharyngeal carcinoma(NPC)and its impact on interferon(IFN)signaling,thioredoxin-interacting protein(TXNIP),and p53 tumor suppressor pathways.Methods HNMT expression in NPC tissues and cell lines was analyzed via qPCR and Western blotting.Functional assays,including cell proliferation,migration,invasion,and apoptosis,were performed after HNMT knockdown or overexpression.Transcriptomic sequencing was used to identify differentially expressed genes(DEGs).In addition,we examined the relationship between HNMT and the IFN/TXNIP/p53 axis via rescue experiments in vitro and in vivo models via qPCR and Western blotting.Results HNMT knockdown reduced cell proliferation,migration,and invasion,and promoted apoptosis in NPC tissues and cell lines.TXNIP was the most significantly upregulated gene following HNMT knockdown.Inhibition of the IFN pathway reversed these effects,confirming the role of HNMT in downregulating the IFN/TXNIP/p53 pathway.An in vivo study revealed that HNMT overexpression correlated with reduced expression of TXNIP and p53 in NCG mice.Conclusion In NPC,HNMT promotes tumor growth and progression by inhibiting the IFN/TXNIP/p53 axis.These findings suggest that targeting the HNMT axis or restoring its function could provide new therapeutic strategies for NPC.展开更多
系统性红斑狼疮(systemic lupus erythematosus, SLE)是一种慢性全身性异质性自身免疫性疾病,其特点是由于免疫系统的失调(包括先天免疫和适应性免疫)、细胞因子上调、补体激活、致病性自身抗体的产生和免疫复合物的沉积,最终导致机体...系统性红斑狼疮(systemic lupus erythematosus, SLE)是一种慢性全身性异质性自身免疫性疾病,其特点是由于免疫系统的失调(包括先天免疫和适应性免疫)、细胞因子上调、补体激活、致病性自身抗体的产生和免疫复合物的沉积,最终导致机体的单个或多个器官先后或同时受损。SLE发病机制错综复杂,临床表现、病程进展及严重程度多样化,这给诊断和治疗均带来一定的挑战。目前干扰素作为SLE发病机制的关键细胞因子已普遍达成共识,干扰素的过量产生不仅发生在已确诊的SLE患者中,还出现在无症状的临床前自身免疫阶段,以此引发了人们对干扰素在SLE信号传导通路及临床应用的极大兴趣和深入研究。所以,明确干扰素的产生、功能及异常免疫调节对SLE的诊治具有深远的意义。在本文中,我们将对有关I型干扰素(IFN-I)在SLE中的产生来源、基因表达、作用机制、临床影响、检测方法及治疗应用展开综述,目的是阐明SLE中I型干扰素的发病机制及治疗进展,希望未来靶向I型干扰素制剂能够为SLE患者带来更行之有效的治疗。Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease characterized by dysregulation of the immune system (including innate and adaptive immunity), cytokine upregulation, complement activation, production of pathogenic autoantibodies, and deposition of immune complexes. Eventually, one or more organs of the body are damaged successively or simultaneously. The pathogenesis of SLE is complex, and the clinical manifestations, course progression and severity of SLE are diverse, which brings certain challenges to diagnosis and treatment. At present, interferon has been widely recognized as a key cytokine in the pathogenesis of SLE. The excessive production of interferon not only occurs in diagnosed SLE patients, but also appears in the asymptomatic preclinical autoimmune stage, which has triggered great interest and in-depth research on the signal pathway and clinical application of interferon in SLE. Therefore, understanding the production, function and abnormal immune regulation of interferon has far-reaching significance for the diagnosis and treatment of SLE. In this paper, we will review the generation source, gene expression, mechanism of action, clinical impact, detection methods and therapeutic application of type I interferon (IFN-I) in SLE, with the purpose of clarifying the pathogenesis and treatment progress of type I interferon in SLE, hoping that targeted type I interferon preparations can bring more effective treatment for SLE patients in the future.展开更多
文摘目的:利用生信分析探讨细胞因子IL-12及IFN-γ对乳腺癌患者免疫微环境的影响,并结合临床病理特征,对其评估新辅助化疗疗效的价值进行研究。方法:在基因表达综合(GEO)数据库中下载GSE163882,比较IL-12相对应基因IL12B及IFN-γ相对应基因IFNG在病理完全缓解(pCR)患者和残留病灶(RD)患者中的表达。收集于我院接受新辅助化疗的50例乳腺癌患者的临床资料,使用卡方检验分析临床病理特征与新辅助化疗疗效的相关性;通过ROC曲线评估血清IL-12、IFN-γ的预测价值,并且确定最佳截断值;采用二元Logistic回归进行多因素分析。通过ssGSEA免疫浸润分析IL12B和IFNG与免疫细胞浸润的相关性;采用GO和KEGG功能富集分析,探讨相关基因潜在生物学功能及信号通路。结果:在GEO数据库GSE163882数据集中IL12B和IFNG在pCR患者中呈现高表达。于我院收治的临床患者中pCR患者化疗前血清IL-12和IFN-γ水平明显高于非pCR组(P γ表达状态显著相关(P γ水平是新辅助化疗疗效的独立影响因素。免疫浸润分析显示,活化CD4 T细胞、活化CD8 T细胞、活化B细胞和自然杀伤细胞在pCR患者中高度浸润。结论:血清IL-12和IFN-γ表达状态与新辅助化疗效果具有相关性,化疗前血清IFN-γ高表达是pCR的独立预测因子。Objective: To investigate the effects of cytokines IL-12 and IFN-γ on the immune microenvironment of breast cancer patients by means of Bioinformatics analysis, and to study their value in evaluating the efficacy of neoadjuvant chemotherapy combined with clinicopathological characteristics. Methods: GSE163882 was downloaded from the Gene Expression Omnibus database, and the expressions of IL-12 corresponding gene IL12B and IFNG corresponding gene IFN-γ were compared in pathologic complete response patients and residual lesion patients. The clinical data of 50 breast cancer patients who received neoadjuvant chemotherapy at The Affiliated Hospital of Qingdao University were collected. Chi-square test was used to analyze the correlation between clinicopathological features and the efficacy of neoadjuvant chemotherapy. The predictive value of serum IL-12 and IFN-γ was evaluated by ROC curve. Multivariate analysis was performed by binary Logistic regression. The correlation between IL12B and IFNG and immune cell infiltration was analyzed by ssGSEA immunoinfiltration. GO and KEGG functional enrichment analysis were used to explore the potential biological functions and signaling pathways of related genes. Results: IL12B and IFNG were highly expressed in pCR patients in the GSE163882 dataset. The serum levels of IL-12 and IFN-γ in pCR patients before chemotherapy were significantly higher than those in non-PCR group (P γ expression after neoadjuvant chemotherapy (P γ level before chemotherapy was an independent factor influencing the efficacy of neoadjuvant chemotherapy. Immunoinfiltration analysis showed that activated CD4 T cells, activated CD8 T cells, activated B cells, and natural killer cells were highly infiltrated in pCR patients. Conclusion: The expression of serum IL-12 and IFN-γ is correlated with the effect of neoadjuvant chemotherapy, and the high expression of serum IFN-γ before chemotherapy is an independent predictor of pCR.
基金supported by grants from Science Research Foundation of Yunnan Education Bureau(No.2023Y0631)Yunnan Provincial Science and Technology Project(No.202303AP140005).
文摘Objective Histamine N-methyltransferase(HNMT)is involved primarily in histamine metabolism,but emerging evidence suggests its potential role in cancer progression.This study investigated the role of HNMT in nasopharyngeal carcinoma(NPC)and its impact on interferon(IFN)signaling,thioredoxin-interacting protein(TXNIP),and p53 tumor suppressor pathways.Methods HNMT expression in NPC tissues and cell lines was analyzed via qPCR and Western blotting.Functional assays,including cell proliferation,migration,invasion,and apoptosis,were performed after HNMT knockdown or overexpression.Transcriptomic sequencing was used to identify differentially expressed genes(DEGs).In addition,we examined the relationship between HNMT and the IFN/TXNIP/p53 axis via rescue experiments in vitro and in vivo models via qPCR and Western blotting.Results HNMT knockdown reduced cell proliferation,migration,and invasion,and promoted apoptosis in NPC tissues and cell lines.TXNIP was the most significantly upregulated gene following HNMT knockdown.Inhibition of the IFN pathway reversed these effects,confirming the role of HNMT in downregulating the IFN/TXNIP/p53 pathway.An in vivo study revealed that HNMT overexpression correlated with reduced expression of TXNIP and p53 in NCG mice.Conclusion In NPC,HNMT promotes tumor growth and progression by inhibiting the IFN/TXNIP/p53 axis.These findings suggest that targeting the HNMT axis or restoring its function could provide new therapeutic strategies for NPC.
文摘系统性红斑狼疮(systemic lupus erythematosus, SLE)是一种慢性全身性异质性自身免疫性疾病,其特点是由于免疫系统的失调(包括先天免疫和适应性免疫)、细胞因子上调、补体激活、致病性自身抗体的产生和免疫复合物的沉积,最终导致机体的单个或多个器官先后或同时受损。SLE发病机制错综复杂,临床表现、病程进展及严重程度多样化,这给诊断和治疗均带来一定的挑战。目前干扰素作为SLE发病机制的关键细胞因子已普遍达成共识,干扰素的过量产生不仅发生在已确诊的SLE患者中,还出现在无症状的临床前自身免疫阶段,以此引发了人们对干扰素在SLE信号传导通路及临床应用的极大兴趣和深入研究。所以,明确干扰素的产生、功能及异常免疫调节对SLE的诊治具有深远的意义。在本文中,我们将对有关I型干扰素(IFN-I)在SLE中的产生来源、基因表达、作用机制、临床影响、检测方法及治疗应用展开综述,目的是阐明SLE中I型干扰素的发病机制及治疗进展,希望未来靶向I型干扰素制剂能够为SLE患者带来更行之有效的治疗。Systemic lupus erythematosus (SLE) is a chronic, heterogeneous autoimmune disease characterized by dysregulation of the immune system (including innate and adaptive immunity), cytokine upregulation, complement activation, production of pathogenic autoantibodies, and deposition of immune complexes. Eventually, one or more organs of the body are damaged successively or simultaneously. The pathogenesis of SLE is complex, and the clinical manifestations, course progression and severity of SLE are diverse, which brings certain challenges to diagnosis and treatment. At present, interferon has been widely recognized as a key cytokine in the pathogenesis of SLE. The excessive production of interferon not only occurs in diagnosed SLE patients, but also appears in the asymptomatic preclinical autoimmune stage, which has triggered great interest and in-depth research on the signal pathway and clinical application of interferon in SLE. Therefore, understanding the production, function and abnormal immune regulation of interferon has far-reaching significance for the diagnosis and treatment of SLE. In this paper, we will review the generation source, gene expression, mechanism of action, clinical impact, detection methods and therapeutic application of type I interferon (IFN-I) in SLE, with the purpose of clarifying the pathogenesis and treatment progress of type I interferon in SLE, hoping that targeted type I interferon preparations can bring more effective treatment for SLE patients in the future.
