同源盒A家族基因在肺鳞癌中的表达谱研究

Expression profile and prognostic value of homebox A family genes in lung squamous cell carcinoma

目的研究同源盒A(homebox A,HOXA)家族基因在肺鳞癌中的表达、预后价值及潜在分子机制。方法利用基因芯片技术检测HOXA家族基因在广西医科大学第一附属医院2017年8月至2017年10月收集的3对肺鳞癌及癌旁组织标本中的表达量,并整合其他多种技术分析计算标准化均数差(SMD)评价HOXA家族基因在1214例肺鳞癌和1139例非癌肺样本中的差异。绘制Kaplan-Meier曲线并通过Cox比例风险分析计算风险率(HR)评价HOXA家族各基因表达对肺鳞癌患者总体生存的影响。使用Pearson检验分析测序数据中HOXA家族基因在肺鳞癌中的甲基化程度与表达值的相关性。结果HOXA9、HOXA10、HOXA7、HOXA1和HOXA13在肺鳞癌中显著高表达(SMD=1.14、0.41、0.61、1.72、1.03);HOXA5在肺鳞癌中显著低表达(SMD=-1.21)。HOXA家族中高表达基因的预后模型具有显著的预后分层价值(HR=1.41,P<0.05)。HOXA家族基因在肺鳞癌中的表达值与甲基化程度呈显著负相关(r=-0.640,P<0.05)。结论HOXA家族基因在肺鳞癌中的表达受异常甲基化的调控。HOXA家族联合预后模型有望应用于肺鳞癌患者的临床预后评估。

Objective To study the expression,prognostic value and potential molecular mechanism of homebox A(HOXA)family genes in lung squamous cell carcinoma(LUSC).Methods The expression levels of HOXA family genes in three pairs of LUSC and adjacent tissues collected from the First Affiliated Hospital of Guangxi Medical University(2017-08 to 2017-10)detected by gene chip technology,and the expression levels of HOXA family genes detected by other technologies were integrated.The heterogeneityand standardized mean difference(SMD)was calculated to evaluate the differential expression of HOXA family genes in 1214 LUSC cases and 1139 non-cancer lung samples.Kaplan-Meier survival curves were drawn and the hazard ratio(HR)was calculated by cox proportional hazards analysis to evaluate the effect of HOXA gene expression on the overall survival of LUSC patients.We also analyzed the correlation between the expression level of HOXA family genes and degree of methylation in LUSC by Pearson test.Results HOXA9,HOXA10,HOXA7,HOXA1 and HOXA13 were significantly overexpressed in LUSC(SMD=1.14,0.41,0.61,1.72,1.03;P<0.05);HOXA5 was significantly under-expressed in LUSC(SMD=-1.21;P<0.05).The combination of HOXA9,HOXA10,HOXA7,HOXA1 and HOXA13 had significant prognostic stratification value(HR=1.41,P<0.01).The expression value of HOXA family genes in LUSC was negatively correlated with the degree of methylation(r=-0.640,P<0.05).Conclusion HOXA family genes may affect the occurrence and development of LUSC by participating in a variety of molecular functions and regulating various signal pathways.HOXA family genes combined with prognostic model is expected to be applied in prognostic prediction of LUSC patients clinically.