文献类型：期刊文献

中文题名：TPD52和TPD52L2在胃癌中异常表达的临床病理特征分析和相关基因共表达意义研究

英文题名：Clinicopathological characterization of aberrant expression of TPD52 and TPD52L2 in gastric cancer and study of the significance of related gene co-expression

作者：高夏青[1];杨春婷[1];郭双铭[1];韩静[2];樊涛[1];杨霄[1];李海龙[1]

第一作者：高夏青

机构：[1]甘肃中医药大学第一临床医学院,甘肃兰州730000;[2]甘肃中医药大学附属医院科研科,甘肃兰州730000

第一机构：甘肃中医药大学临床医学院

年份：2024

卷号：28

期号：4

起止页码：379

中文期刊名：中国实验诊断学

外文期刊名：Chinese Journal of Laboratory Diagnosis

收录：CSTPCD

基金：甘肃省卫生健康行业科研计划项目(GSWSKY2021-009);高等学校创新创业训练计划国家级项目(甘中医大创发[2022]8号)

语种：中文

中文关键词：TPD52;TPD52L2;胃癌;病理特征;预后;生物信息学

外文关键词：TPD52;TPD52L2;gastric cancer;pathological characteristics;prognosis;bioinformatics

摘要：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。
Objective To investigate the clinicopathological characteristics of tumor protein D52(TPD52)and tumor protein D52-like 2(TPD52L2)aberrantly expressed in gastric cancer by applying bioinformatics methods,and to analyze the significance of related gene co-expression.Methods Based on data obtained from the cancer genome atlas(TCGA),the R language package was used to compare the correlation between the differential expression of TPD52 and TPD52L2 in gastric cancer tissues and paraneoplastic tissues with clinicopathological features and explore the situation with the level of immune cell infiltration,Kaplan-Meier survival analysis and Cox regression to assess the relationship between the expression of TPD52 and TPD52L2 and patient prognosis.Immunohistochemistry of TPD52 and TPD52L2 in gastric cancer tissues was analyzed using the Human Protein Atlas database.Co-expressed genes of TPD52 and TPD52L2 were analyzed with the help of cBioPortal database and enriched with Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis using SangerBox platform.Protein-protein interaction(PPI)network was established by STRING database for co-expressed genes,and Cytoscape 3.9 was used to screen core co-expressed genes and further validate the survival and relevance of core co-expressed genes.Results The expression levels of both TPD52 and TPD52L2 were significantly higher in gastric cancer tissues than in paraneoplastic tissues and were closely associated with pathological stage,histological grade,H.pylori infection,and Barretts esophagus.TPD52 expression correlated with the abundance of infiltration of cells such as Th2 and NK cells,and TPD52L2 expression correlated with the abundance of infiltration of cells such as Th2 and Mast cells.The low expression group had longer overall survival(OS),first progression survival(FP),and re-progression survival(PPS)compared to the TPD52L2 high expression group.The results of univariate Cox analysis showed that the expression of TPD52 and TPD52L2 correlated with TNM stage and pathological stage and poor prognosis of gastric cancer patients,and the results of multifactorial Cox analysis showed that M stage was an independent risk factor for OS of gastric cancer patients.KEGG enrichment analysis revealed that co-expressed genes of TPD52 were involved in signaling pathways such as metabolic pathway and transcriptional misregulation in cancer,and co-expressed genes of TPD52L2 were involved in signaling pathways such as pathway in cancer and spliceosome.The results of core gene survival analysis in the PPI network showed that PLCG1,PRKACA,MAPK11,NGFR,and HSP90AB1 in the high expression group had a poor prognosis,and correlation analysis revealed that MAPK11,CYCS,and NGFR were the most closely related genes to TPD52,and RUVBL1,NOP56,HSP90AB1,and CCT6A were the most closely related genes to TPD52L2,which can be used as candidate genes to explore the involvement of TPD52 and TPD52L2 in the malignant biological behavior of gastric cancer.Conclusion TPD52 and TPD52L2 are highly expressed in gastric cancer tissues and play an important role in the development of gastric cancer,and are expected to be biomarkers and therapeutic targets for the early diagnosis and prognosis of gastric cancer.