利用GEO公共数据集分析CHAF1A在肿瘤中的表达及临床意义

Analysis of the expression of chromatin assembly factor 1 subunit A in multiple tumors and its clinical signii cance by utilizing GEO datasets

目的 :研究染色体组装因子1单位A(chromatin assembly factor 1,subunit A,CHAF1A)在人体多种肿瘤中的表达情况,探讨CHAF1A与肝细胞癌、乳腺癌和肺癌临床病理特征的关系,并评价检测CHAF1A表达对肝细胞癌、乳腺癌和肺癌预后评估的意义。方法 :从美国国立生物技术信息中心(National Center for Biotechnology Information,NCBI)网站收集与CHAF1A表达及人类肿瘤相关的基因表达汇编(Gene Expression Omnibus,GEO)公共数据集,下载这些肿瘤样本表达谱资料及其对应的临床信息。采用χ2检验分析CHAF1A表达与肿瘤患者临床病理指标的相关性,Kaplan-Meier法进行总生存和无复发生存期分析。采用基因集富集分析(gene set enrichment analysis,GSEA)方法分析预测受CHAF1A调控的相关基因。结果 :CHAF1A在肝细胞癌、结直肠癌、食管癌、肺癌、卵巢癌、黑素瘤、鼻咽癌和胃癌中均高表达(P<0.05)。CHAF1A表达与乳腺癌患者的p53基因缺失、p53基因突变、雌激素受体表达、孕激素受体表达以及Elston组织学分级密切相关(P<0.05),与肺癌患者的年龄、性别、T分期、淋巴结浸润和远端转移密切相关(P<0.05),而在肝细胞癌、乳腺癌和肺癌中与患者手术预后相关(P<0.05)。CHAF1A可能调控与细胞周期调控、DNA复制以及细胞骨架调节相关的基因集。结论 :CHAF1A在多种肿瘤中高表达,推测其可以作为潜在的判断肿瘤患者预后的标志物以及治疗肿瘤的靶标。

Objective： To investigate the expression status of chromatin assembly factor 1, subunit A （CHAF1A） in human multiple tumors, clarify the relationship between CHAF1A expression and clinicopathological features of patients with hepatocellular carcinoma, breast cancer and lung cancer, and evaluate the function of CHAF1A as a prognostic marker in these cancers. Methods： GEO （Gene Expression Omnibus） datasets were collected from National Center for Biotechnology Information （NCBI） website. The tumor sample expression profile including CHAF1A expression data and its clinical information were downloaded. The correlation between CHAF1A gene expression and the clinicopathologic features was analyzed by Chi-square test. Overall survival and recurrence-free survival were analyzed by Kaplan-Meier method. GSEA （gene set enrichment analysis） was used to predict the gene sets modulated by CHAF1A. Results： The expressions of CHAF1A were up-regulated in hepatocellular carcinoma, colorectal cancer, esophageal carcinoma, lung cancer, ovarian cancer, melanoma, nasopharyngeal carcinoma and gastric cancer （all P 〈 0.05）. CHAF1A expression was associated with p53 deficiency, p53 mutation, estrogen receptor （ER） expression, progesterone receptor （PR） expression and Elston histologic grade in patients with breast cancer （all P 〈 0.05）, and it was also associated with the age, gender, T stage, lymph node metastasis and distant metastasis in patients with lung cancer （all P 〈 0.05）. High level of CHAF1A expression indicated poor prognosis of patients with hepatocellular carcinoma, breast cancer and lung cancer （all P 〈 0.05）. CHAF1A could regulate gene sets involving cell cycle regulation, DNA replication and cytoskeleton regulation. Conclusion： CHAF1A is highly expressed in multiple tumors, and it maybe used as a potential prognostic marker and a therapeutic target.