机构地区:[1]天津市肿瘤医院骨与软组织肿瘤科国家肿瘤临床医学研究中心天津市“肿瘤防治”重点实验室天津市恶性肿瘤临床医学研究中心,天津300060 [2]国家癌症中心国家肿瘤临床医学研究中心中国医学科学院北京协和医学院肿瘤医院深圳医院骨科,广东深圳518116 [3]天津市天津医院骨与软组织肿瘤科,天津300211
出 处:《中国修复重建外科杂志》2024年第10期1220-1228,共9页Chinese Journal of Reparative and Reconstructive Surgery
摘 要:目的基于临床组织样本分析,探讨细胞周期蛋白依赖性激酶1(cell-cycle dependent kinase 1,CDK1)及其上下游分子在恶性周围神经鞘瘤(malignant peripheral nerve sheath tumor,MPNST)发生发展过程中的角色及其临床意义。方法选取2011年9月-2020年3月接受手术切除治疗,并经组织学、病理学证实的56例MPNST患者肿瘤样本(“Tianjin”数据集)以及17例正常组织样本作为研究对象。通过转录组测序、生物信息学分析、免疫组织化学染色以及生存分析的方法,对MPNST相关枢纽基因进行筛选,并基于枢纽基因的表达水平及预后关联进行分析探讨。结果转录组测序与生物信息学分析发现,MPNST中表达上调的基因更多地富集在细胞周期相关通路中,而CDK1在所有得到的差异表达基因中居于枢纽地位。进一步差异分析结果表明,CDK1 mRNA的表达水平在肉瘤组织中显著高于正常组织[基于检索癌症基因组图谱(TCGA)数据库,P<0.05];而在MPNST组织中CDK1 mRNA的表达水平不但显著高于正常组织(基于Tianjin、GSE141438数据集,P<0.05),且显著高于神经纤维瘤(neurofibromatosis,NF)和丛状神经纤维瘤(plexiform neurofibromas,PNF)(基于GSE66743和GSE145064数据集,P<0.05)。免疫组织化学染色结果表明CDK1蛋白在MPNST组织中表达率为40.31%。生存分析结果显示CDK1表达与患者较差的预后相关,MPNST患者中CDK1 mRNA高表达组的生存时间显著低于低表达组(P<0.05),CDK1蛋白阳性表达患者整体生存趋势较CDK1阴性表达患者差。此外,对CDK家族基因(CDK1~8)的差异分析发现,只有CDK1在MPNST、NF、PNF的表达均显著上调(P<0.05)。结论CDK1表达增高与MPNST患者较差的预后相关。相比其他CDK家族成员,CDK1表现出独特表达模式,提示其作为MPNST潜在治疗靶点的前景。Objective To explore the role and clinical significance of cell-cycle dependent kinase 1(CDK1)and its upstream and downstream molecules in the development of malignant peripheral nerve sheath tumor(MPNST)through the analysis of clinical tissue samples.Methods A total of 56 tumor samples from MPNST patients(“Tianjin”dataset)who underwent surgical resection,confirmed by histology and pathology between September 2011 and March 2020,along with 17 normal tissue samples,were selected as the research subjects.MPNST-related hub genes were identified through transcriptome sequencing,bioinformatics analysis,immunohistochemistry staining,and survival analysis,and their expression levels and prognostic associations were analyzed.Results Transcriptome sequencing and bioinformatics analysis revealed that upregulated genes in MPNST were predominantly enriched in cell cycle-related pathways,with CDK1 occupying a central position among all differentially expressed genes.Further differential analysis demonstrated that CDK1 mRNA expression in sarcoma tissues was significantly higher than in normal tissues[based on searching the cancer genome atlas(TCGA)dataset,P<0.05].In MPNST tissues,CDK1 mRNA expression was not only significantly higher than in normal tissues(based on Tianjin,GSE141438 datasets,P<0.05),but also significantly higher than in neurofibromatosis(NF)and plexiform neurofibromas(PNF)(based on GSE66743 and GSE145064 datasets,P<0.05).Immunohistochemical staining results indicated that the expression rate of CDK1 protein in MPNST tissues was 40.31%.Survival analysis results demonstrated that CDK1 expression was associated with poor prognosis.The survival time of MPNST patients with high CDK1 mRNA expression was significantly lower than that of the low expression group(P<0.05),and the overall survival trend of patients with positive CDK1 protein expression was worse than that of patients with negative CDK1 expression.Additionally,differential analysis of CDK family genes(CDK1-8)revealed that only CDK1 was significantly u
关 键 词:恶性周围神经鞘瘤 细胞周期依赖性蛋白激酶1 转录组测序 生物信息学分析 预后
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