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肺腺癌患者KIF11表达水平及临床意义

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目的:分析KIF11 基因在肺腺癌组织的表达水平及其对肺腺癌患者生存预后的影响,初步探讨可能的作用机制.方法:利用生物信息学方法分析TCGA和GEO数据库中肺腺癌患者KIF11 mRNA表达及信号通路富集情况.采用Kaplan-Meier曲线分析KIF11 mRNA的表达水平对患者总生存时间的影响.利用单因素及多因素Cox回归分析方法分析TCGA数据库中影响肺腺癌患者预后的因素,并评估KIF11 与Ki-67 表达水平的关系.收集 60 对某院收治的肺腺癌患者癌组织及癌旁正常组织标本,利用免疫组化方法检测KIF11 蛋白和Ki-67 表达水平,分析KIF11 蛋白表达水平与患者临床病理因素的关联性.流式细胞术检测KIF11 对肺腺癌细胞周期分布的影响.结果:TCGA和GEO数据库中癌组织KIF11 mRNA表达水平均高于正常组织,差异有统计学意义(P<0.05).Kaplan-Meier生存分析结果显示,KIF11 mRNA高表达组患者生存时间短于低表达组(P<0.05).免疫组化结果显示,肺腺癌患者癌组织 KIF11 和 Ki-67 蛋白表达均高于癌旁组织,差异有统计学意义(P<0.05).多因素Cox回归分析显示,肺腺癌的预后与T分期、是否淋巴结转移及KIF11 mRNA表达水平有关.KIF11 mRNA高表达组肿瘤直径>3 cm、发生淋巴结转移、分化程度为高分化、Ki-67 高表达患者比例高于KIF11 mRNA低表达组,肿瘤分期为Ⅰ期的患者比例低于KIF11 mRNA低表达组,差异均有统计学意义(P<0.05).KIF11 蛋白与Ki-67 表达水平呈正相关(P<0.05).KIF11 基因GO富集及KEGG分析结果显示,KIF11 基因在细胞分裂、DNA复制信号通路上功能富集.基因干扰试验显示,干扰肺腺癌细胞A549 及H1975 细胞的KIF11 基因表达后,肺腺癌细胞的G1 期细胞比例增加,S期细胞比例减少(P<0.05).结论:肺腺癌组织KIF11 表达水平明显高于正常组织,其高表达与肺腺癌患者预后有关,可能通过调节肺腺癌细胞周期、促进细胞增殖机制发挥作用,KIF11 可作为肺腺癌患者的治疗靶点和预后评估的潜在标志物.
Expression level of KIF11 in patients with lung adenocarcinoma and its clinical significance
Objective:To study the expression level and prognostic significance of KIF11 gene in lung adenocarcinoma tissue and explore its possible mechanism of KIF11 in the cancer.Methods:Bioinformatics methods were used to analyze KIF11 mRNA expression and signaling pathway enrichment in lung adenocarcinoma patients in TCGA and GEO databases.Kaplan-Meier curve was applied to analyze the impact of KIF11 mRNA expression level on patients'overall survival time.Single-factor and multi-factor Cox regression a-nalysis methods were taken to analyze the factors affecting the prognosis of patients with lung adenocarcinoma in the TCGA database,and the relationship between the expression levels of KIF11 and Ki-67 in the TCGA database was assessed.Lung cancer tissues and ad-jacent normal tissue specimens from 60 pairs of lung adenocarcinoma patients admitted to a hospital were collected.Immunohistochem-istry was used to detect the expressions of KIF11 protein and Ki-67,and the correlation between KIF11 protein expression level and va-rious clinicopathological factors of the patients was analyzed.Flow cytometry was adopted to detect the effect of KIF11 on the cycle dis-tribution of lung adenocarcinoma cells.Results:The expression levels of KIF11 mRNA in cancer tissues in the TCGA database and GEO database were higher than those in the normal tissues,the differences being statistically significant(P<0.05).Kaplan-Meier survival analysis results showed that the survival time of the patients in the high expression group of KIF11 mRNA was shorter than that of the patients in the lower expression group(P<0.05).Immunohistochemistry result denoted that the protein expressions of KIF11 and Ki-67 in lung cancer tissues were all higher than those in adjacent tissues(P<0.05).Univariate and multivariate Cox regression analysis indicated that there was a significant statistical difference between the expression level of KIF11 mRNA and tumor size,lymph node metastasis,T stage,degree of differentiation and Ki-67 expression level,indicating a poor prognosis of the patient(P<0.05).Rates of patients with diameter of tumor>3 cm,lymph node metastasis,high degree of differentiation,and high expression of Ki-67 in the high expression group of KIF mRNA were higher than those in the low expression group of KIF mRNA,and rate of patients in tumor stage Ⅰ was lower than that in the low expression group of KIF mRNA(P<0.05).KIF11 protein was positively correlated with the expression level of Ki-67(P<0.05).The results of KIF11 gene GO enrichment analysis and KEGG analysis suggested that KIF11 gene was related to cell division and DNA replication signaling pathways.After inter-fering with KIF11 gene expression in lung adenocarcinoma cells A549 and H1975 cells,the proportion of G1 phase cells in lung adeno-carcinoma cells increased and the proportion of S phase cells decreased(P<0.05).Conclusion:The expression level of KIF11 in lung adenocarcinoma is significantly higher than that in normal tissues.The high expression is related to the clinical stage and poor prognosis of patients,which may be related to its regulation of the cycle distribution of lung adenocarcinoma cells and promotion of cell prolifera-tion.KIF11 is a potential marker for prognosis and treatment of lung adenocarcinoma.

Lung adenocarcinomaKIF11Expression levelPrognosisCell cycle

陶累累、陈平、马靓、严文跃、钱琦、赵霞

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江苏省盐城市第一人民医院 肿瘤内科,224008

肺腺癌 KIF11 表达水平 预后 细胞周期

盐城市医学科技发展计划(2020)

YK2020024

2024

淮海医药
蚌埠市医学科学情报站 《淮海医药》编辑部

淮海医药

影响因子:0.58
ISSN:1008-7044
年,卷(期):2024.42(3)
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