肺腺癌组织FAM83A基因表达与预后相关性

Effect of FAM83A gene expression on the prognosis of lung adenocarcinoma

目的肺癌是全球发病率和死亡率最高的恶性肿瘤之一,人类编码的FAM83A基因在肺癌中高表达。本研究探讨FAM83A基因表达与肺腺癌进展和转移关系,为临床肺腺癌治疗提供潜在靶点。方法所有用于生物信息分析的数据均来自癌症数据库TCGA,Bioedit软件用于不同物种FAM83A蛋白保守型对比和分析;信号通路分析软件GSEA预测FAM83A基因调控KRAS信号通路是否参与肺腺癌进展。结果生物信息分析显示FAM83A蛋白有一个300碱基左右的保守功能区域。肺腺癌患者中FAM83A基因表达量排在所有升高基因第2位。A-431细胞染色结果提示该基因主要位于细胞核;RNA-seq表达数据分析提示FAM83A基因在肺腺癌患者中表达高于正常对照组,差异有统计学意义,t=5.46,P<0.001。随着肿瘤级别增加FAM83A表达逐渐增加,但差异无统计学意义,FAM83A基因高表达患者预后差于低表达患者,Z=2.16,P<0.001;吸烟患者FAM83A基因表达高于正常对照组,t=3.45,P<0.001。吸烟与非吸烟患者中FAM83A基因表达差异无统计学意义,FAM83A高表达合并吸烟患者中预后较一般患者更差,t=3.84,P<0.001。通路"Singh KRAS dependency signature"在肺腺癌患者组织明显富集(NES=1.79,P=0.004,FDR q=4.79×10-4),富集分数为0.6。结论 FAM83A基因表达可能与肺腺癌进展及预后密切相关,并可能成为临床肺腺癌治疗的重要干预靶点。

OBJ ECTIVE Lung cancer is one of the most common malignant tumor with high incidence of morbidity and mortality in the world.The human encoded FAM83A gene is highly expressed in lung cancer.Hence,investigate the relationship between RNA-seq expression of FAM83A and the progression and metastasis of lung adenocarcinoma may provide a target for clinical treatment.METHODS All the data used for bioinformatics analysis were downloading from TCGA database,Bioedit software was used for comparison and analysis of FAM83A proteins of the conservative alignment from different species.GSEA software was employed to predict the importance of FAM83A in the development of lung adenocarcinoma.RESULTS Bioinformatics analysis indicated that FAM83A protein had a conservative functional region ranging about 300 bp.The expression level of FAM83A gene in lung adenocarcinoma patients ranked second in all elevated genes.The results of A-431 cell staining indicated that the gene was mainly located in the nucleus;RNA-seq expression data analysis indicated that the expression of FAM83A gene in lung adenocarcinoma patients was higher than that in the normal control group,effectively,Z=5.46,P<0.001.The expression of FAM83A increased gradually with the increase of tumor grade,but the difference was not statistically significant.The prog nosis of patients with high expression of FAM83A gene was worse than that of patients with low expression,Z=2.16,P<0.001.The expression of FAM83A gene in smoking patients was higher than that of normal control group,t=3.45,P<0.001.There was no significant difference in FAM83A gene expression between smokers and non-smokers.The prognosis of patients with high FAM83A expression and smoking was worse than that of the general patients,t=3.84,P<0.001.The pathway“Singh KRAS dependency signature”was significantly enriched in patients with lung adenocarcinoma(NES=1.79,P=0.004,FDR q=4.79×10^-4),and the enrichment score was 0.6.CONCLUSION The expression of FAM83A gene is closely related to the progression and prognosis of lung adenocarcinoma and may become an important intervention target for the treatment of lung adenocarcinoma.