基于生物信息学分析KIF14在肾透明细胞癌的表达、功能及临床意义

Bioinformatic analysis of the expression of KIF14 and its clinical significance and biological functions in clear cell renal cell carcinoma

目的探究驱动蛋白家族成员14(KIF14)在肾透明细胞癌(ccRCC)中的表达及其与临床预后、免疫浸润的关系。方法运用TCGA、GEO数据库和Ualcan数据库分析KIF14在ccRCC的表达与不同临床病理特征之间的相关性;Kaplan-Meier曲线分析KIF14表达与临床预后的相关性;Timer数据库分析KIF14表达与免疫细胞浸润的相关性;Genemania数据库构建KIF14蛋白相互作用网络;Linkedomics数据库分析与KIF14表达相关的基因并使用R语言进行GO和KEGG分析。体外功能学试验验证KIF14的生物学功能。结果KIF14在ccRCC中高表达并与临床分期、病理分级以及淋巴转移呈正相关,与患者的预后负相关,KIF14的表达是ccRCC患者总生存期的独立危险因素。GO分析提示KIF14参与了DNA复制,细胞核分裂,细胞器裂变,以及细胞粘附等生物学过程。KEGG信号通路提示KIF14参与了细胞周期,p53信号通路等过程。Genemania提示KIF14主要与CENPE、CIT、KIF23等蛋白存在相互作用。Timer发现KIF14的表达与免疫细胞浸润呈正相关。敲低KIF14表达可以抑制ccRCC细胞的增殖、迁移和侵袭潜能。结论KIF14可能成为肾透明细胞癌新的预后标志物和潜在的临床治疗靶点。

Objective To investigate the expression of Kinesin family member 14(KIF14),and its correlation with clinical prognosis and immune cell infiltration of clear cell renal cell carcinoma(ccRCC).Methods The correlation between KIF14 expression in ccRCC and different clinicopathological features were analyzed with TCGA,GEO and Ualcan databases.The correlation between KIF14 expression and prognosis was analzyed with Kaplan-Meier method.The correlation between KIF14 expression and immune cell infiltration was analzyed with TIMER.The protein-protein interaction network of KIF14 was conducted with Genemania.The co-expression genes of KIF14 in TCGA-KIRC were picked out in Linkedomics database and were used to perform GO annotations and KEGG pathway enrichment analysis with R software.The biological functions of KIF14 were verified with in vitro functional assay.Results KIF14 was highly expressed in ccRCC tissue and was positively correlated with clinical stage,pathological grade,and lymphatic metastasis,but negatively correlated with clinical prognosis.KIF14 expression was an independent risk factor for overall survival of ccRCC patients.GO annotations showed that KIF14 was involved in DNA replication,nuclear division,organelle fission,and cell adhesion.KEGG pathway enrichment analysis showed that KIF14 participated in cell cycle and p53 signaling pathway.Genemania analysis indicated KIF14 interacted with CENPE,CIT,KIF23,and other proteins.Timer showed that KIF14 was positively correlated with immune cell infiltration.Knockdown of KIF14 expression suppressed cell proliferation,migration,and invasion of ccRCC.Conclusions KIF14 may serve as a novel prognostic marker and a potential therapeutic target of clear cell renal cell carcinoma.