乳腺癌中KIF4A基因表达的临床意义及基因富集分析

Expression and Clinical Significances of Kinesin Family Member 4A in Breast Cancer with Gene Sets Enrichment Analysis

目的探讨驱动蛋白超家族4A(kinesin family member 4A,KIF4A)在乳腺癌中的表达及与临床病理特征、预后的关系。方法利用GEO数据库的GSE3494公共数据集和TCGA数据库的乳腺癌样本及其临床资料,采用χ2检验进行KIF4A与临床病理特征的相关性分析,Kaplan-Meier法进行生存分析。通过基因富集分析预测乳腺癌中高表达KIF4A所富集的基因集。结果 KIF4A在不同Elston组织学分级和TNM分期的乳腺癌肿瘤样本中表达差异有统计学意义(P=0.000)。GSE3494和TCGA数据库中KIF4A与ER水平、PR水平均显著相关(P=0.000);与年龄仅TCGA数据库分析结果差异有统计学意义(P=0.000)。此外,GSE3494数据集中,KIF4A与肿瘤大小、淋巴结浸润均显著相关(P=0.000);TCGA数据库中,KIF4A仅与T分期显著相关(P=0.000),与N分期(P=0.081)、M分期(P=0.372)均不相关。KIF4A高表达的乳腺癌患者预后较差,其疾病特异生存期(P=0.001)和总体生存率(P=0.005)均远低于KIF4A低表达患者,且富集了与细胞分裂、细胞周期调控、DNA复制及DNA损伤修复有关的基因集。结论 KIF4A与乳腺癌多个临床病理指标相关,可作为潜在的乳腺癌预后标志物和治疗靶标进一步研究。

Objective To explore the expression of KIF4A gene in breast cancer and clarify its relationship between clinicopathological features and prognosis. Methods The expression data of the breast cancer samples accompanied with clinical information in GEO dataset（GSE3494）and TCGA dataset were collected. Chi-square test was performed to find the correlation of KIF4A expression with clinicopathologic characteristics and Kaplan-Meier method was used for survival analysis. GSEA was conducted to predict the gene sets regulated by KIF4A in breast cancer. Results The differential expression of KIF4A was significant in different Elston histologic grades and TNM stages （P=0.000）. KIF4A expression was significantly associated with ER status and PR status （P=0.000） weather in GSE3494 or TCGA dataset. It was related with age only in TCGA （P=0.000）. Besides, KIF4A was significantly associated with tumor size and lymph node status （P=0.000） in GSE3494 data set, and in TCGA dataset, KIF4A was significantly related with T stage（P=0.000） instead of N stage （P=0.081） and M stage （P=0.372）. Higher expression of KIF4A showed a poor prognosis in breast cancer with the poor disease-specific survival （P=0.001） and overall survival （P=0.005）. It also regulated gene sets related to cell division, cell cycle, DNA replication and DNA damage repair. Conclusion The expression of KIF4A is related to multiple clinicopathological features and indicates a poor prognosis. It may be used as a potential prognostic marker for breast cancer.