目的应用生物信息学的方法探讨肿瘤蛋白D52(tumor protein D52,TPD52)和肿瘤蛋白D52样2(tumor protein D52-like 2,TPD52L2)在胃癌中异常表达的临床病理特征,并分析相关基因共表达的意义。方法基于癌症基因组图谱(The Cancer Genome AHa...目的应用生物信息学的方法探讨肿瘤蛋白D52(tumor protein D52,TPD52)和肿瘤蛋白D52样2(tumor protein D52-like 2,TPD52L2)在胃癌中异常表达的临床病理特征,并分析相关基因共表达的意义。方法基于癌症基因组图谱(The Cancer Genome AHas,TCGA)获取数据,利用R语言软件包比较TPD52和TPD52L2在胃癌组织和癌旁组织中的差异表达与临床病理特征的相关性,并探索与免疫细胞浸润水平的情况,Kaplan-Meier生存分析和Cox回归评估TPD52和TPD52L2的表达与患者预后的关系。利用Human Protein Atlas数据库分析TPD52和TPD52L2在胃癌组织中的免疫组化染色情况。借助cBioPortal数据库分析TPD52和TPD52L2的共表达基因,并使用SangerBox平台进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。通过STRING数据库对共表达基因建立蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,使用Cytoscape 3.9筛选核心共表达基因,并进一步验证核心共表达基因的生存期和相关性。结果胃癌组织中TPD52和TPD52L2的表达水平均明显高于癌旁组织,并与病理分期、组织学分级、幽门螺旋杆菌感染和Barretts食管密切相关。TPD52的表达与Th2和NK细胞等细胞的浸润丰度相关,TPD52L2的表达与Th2和肥大细胞等细胞的浸润丰度相关。与TPD52L2高表达组相比,低表达组有更长的总生存期(OS)、首次进展生存期(FP)和再次进展生存期(PPS)。单因素Cox分析结果表明,TPD52和TPD52L2的表达与TNM分期、病理分期及胃癌患者的预后不良相关,多因素Cox分析结果表明,M分期是影响胃癌患者OS的独立危险因素。KEGG富集分析发现TPD52的共表达基因参与了代谢通路和癌症的转录失调等信号通路,TPD52L2的共表达基因参与了癌症通路和剪接体等信号通路。PPI网络中核心基因生存分析结果表明,高表达组的PLCG1、PRKACA、MAPK11、NGFR和HSP90AB1预后较差,相关性分析发现MAPK11、CYCS和NGFR是与TPD52关系最紧密的基因,RUVBL1、NOP56、HSP90AB1和CCT6A是与TPD52L2关系最紧密的基因,可作为探讨TPD52和TPD52L2参与胃癌恶性生物学行为的候选基因。结论TPD52和TPD52L2在胃癌组织中高表达,且在胃癌的发生发展中发挥着重要作用,有望成为胃癌早期诊断和预后的生物标志物和治疗靶点。展开更多
Background:Colon adenocarcinoma(COAD)is the second leading cause of cancer death worldwide thus,identification of COAD biomarkers is critical.Mitotic Arrest Deficient 2 Like 2(MAD2L2)is a key factor in mammalian DNA d...Background:Colon adenocarcinoma(COAD)is the second leading cause of cancer death worldwide thus,identification of COAD biomarkers is critical.Mitotic Arrest Deficient 2 Like 2(MAD2L2)is a key factor in mammalian DNA damage repair and is highly expressed in many malignant tumors.This is a comprehensive study of MAD2L2 expression,its diagnostic value,prognostic analysis,potential biological function,and impact on the immune system of patients with COAD.Methods:Gene expression,clinical relevance,prognostic analysis,diagnostic value,GO/KEGG cluster analysis,data obtained from TCGA,and bioinformatics statistical analysis were performed using the R package.Immune responses to MAD2L2 expression in COAD were analyzed using TIMER.The expression of MAD2L2 in HCT116 cells induced by the inflammatory factor TNF-αwas detected using Western blot.Results:Our results underscore the clinical diagnostic value and potential biological significance of MAD2L2 in patients with COAD.A high level of MAD2L2 expression has been found in COAD and correlated with tumor status and colon polyps.ROC curve analysis showed that MAD2L2 expression has high diagnostic value in COAD.Analysis of immune infiltration results showed that MAD2L2 expression was positively correlated with neutrophil levels.The western blot results demonstrated that MAD2L2 was dose-dependently present with TNF-α.GO/KEGG revealed that MAD2L2 overexpressed and coexpressed genes were mostly involved in biological functions,including hypoxia response,response to reduced oxygen levels,mitochondrial translation elongation,and other processes.Conclusion:MAD2L2 as a new COAD biomarker contributes to our understanding of how alterations in gene expression and the immunological environment contribute to the development of colon cancer.Following further investigation,MAD2L2 may prove to be a viable target factor for clinical diagnosis and therapy of COAD.展开更多
文摘目的应用生物信息学的方法探讨肿瘤蛋白D52(tumor protein D52,TPD52)和肿瘤蛋白D52样2(tumor protein D52-like 2,TPD52L2)在胃癌中异常表达的临床病理特征,并分析相关基因共表达的意义。方法基于癌症基因组图谱(The Cancer Genome AHas,TCGA)获取数据,利用R语言软件包比较TPD52和TPD52L2在胃癌组织和癌旁组织中的差异表达与临床病理特征的相关性,并探索与免疫细胞浸润水平的情况,Kaplan-Meier生存分析和Cox回归评估TPD52和TPD52L2的表达与患者预后的关系。利用Human Protein Atlas数据库分析TPD52和TPD52L2在胃癌组织中的免疫组化染色情况。借助cBioPortal数据库分析TPD52和TPD52L2的共表达基因,并使用SangerBox平台进行京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析。通过STRING数据库对共表达基因建立蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,使用Cytoscape 3.9筛选核心共表达基因,并进一步验证核心共表达基因的生存期和相关性。结果胃癌组织中TPD52和TPD52L2的表达水平均明显高于癌旁组织,并与病理分期、组织学分级、幽门螺旋杆菌感染和Barretts食管密切相关。TPD52的表达与Th2和NK细胞等细胞的浸润丰度相关,TPD52L2的表达与Th2和肥大细胞等细胞的浸润丰度相关。与TPD52L2高表达组相比,低表达组有更长的总生存期(OS)、首次进展生存期(FP)和再次进展生存期(PPS)。单因素Cox分析结果表明,TPD52和TPD52L2的表达与TNM分期、病理分期及胃癌患者的预后不良相关,多因素Cox分析结果表明,M分期是影响胃癌患者OS的独立危险因素。KEGG富集分析发现TPD52的共表达基因参与了代谢通路和癌症的转录失调等信号通路,TPD52L2的共表达基因参与了癌症通路和剪接体等信号通路。PPI网络中核心基因生存分析结果表明,高表达组的PLCG1、PRKACA、MAPK11、NGFR和HSP90AB1预后较差,相关性分析发现MAPK11、CYCS和NGFR是与TPD52关系最紧密的基因,RUVBL1、NOP56、HSP90AB1和CCT6A是与TPD52L2关系最紧密的基因,可作为探讨TPD52和TPD52L2参与胃癌恶性生物学行为的候选基因。结论TPD52和TPD52L2在胃癌组织中高表达,且在胃癌的发生发展中发挥着重要作用,有望成为胃癌早期诊断和预后的生物标志物和治疗靶点。
基金supported by the Ningxia Hui Autonomous Region Key Research and Development Program(Grant No.2021BEG03084).
文摘Background:Colon adenocarcinoma(COAD)is the second leading cause of cancer death worldwide thus,identification of COAD biomarkers is critical.Mitotic Arrest Deficient 2 Like 2(MAD2L2)is a key factor in mammalian DNA damage repair and is highly expressed in many malignant tumors.This is a comprehensive study of MAD2L2 expression,its diagnostic value,prognostic analysis,potential biological function,and impact on the immune system of patients with COAD.Methods:Gene expression,clinical relevance,prognostic analysis,diagnostic value,GO/KEGG cluster analysis,data obtained from TCGA,and bioinformatics statistical analysis were performed using the R package.Immune responses to MAD2L2 expression in COAD were analyzed using TIMER.The expression of MAD2L2 in HCT116 cells induced by the inflammatory factor TNF-αwas detected using Western blot.Results:Our results underscore the clinical diagnostic value and potential biological significance of MAD2L2 in patients with COAD.A high level of MAD2L2 expression has been found in COAD and correlated with tumor status and colon polyps.ROC curve analysis showed that MAD2L2 expression has high diagnostic value in COAD.Analysis of immune infiltration results showed that MAD2L2 expression was positively correlated with neutrophil levels.The western blot results demonstrated that MAD2L2 was dose-dependently present with TNF-α.GO/KEGG revealed that MAD2L2 overexpressed and coexpressed genes were mostly involved in biological functions,including hypoxia response,response to reduced oxygen levels,mitochondrial translation elongation,and other processes.Conclusion:MAD2L2 as a new COAD biomarker contributes to our understanding of how alterations in gene expression and the immunological environment contribute to the development of colon cancer.Following further investigation,MAD2L2 may prove to be a viable target factor for clinical diagnosis and therapy of COAD.
