利用生物信息学分析LMO2在乳腺癌中的表达和功能

Bioinformatics approach to analyze LMO2 expression and function in breast cancer

目的探讨LMO2在乳腺癌中的表达及其共表达基因的生物学作用。方法通过Oncomine数据库挖掘LMO2在多种肿瘤中的表达水平,并基于基因表达谱数据动态分析(GEPIA)及人类蛋白质表达图谱(HPA)数据库检索LMO2在乳腺癌组织与正常组织中的表达差异。采用KM plotter数据库评估LMO2在乳腺癌中的预后价值。利用Coexpedia数据库构建LMO2在乳腺癌中的共表达基因网络,并用FunRich软件对score>3的共表达基因注释;通过GEPIA筛选出差异有统计学意义的关键基因,进一步分析LMO2与这些关键基因的相关性,并对这些基因进行京都基因与基因组百科全书(KEGG)富集。结果乳腺癌组织中,LMO2 mRNA和蛋白表达较正常乳腺组织均明显下调(P<0.05),LMO2低表达预示着乳腺癌患者更差的预后。LMO2的共表达基因主要有ADGRL4、GIMAP6、PECAM1、TGFBR2、MEF2C、CD93、S1PR1、LHFP、GMFG、A2M、LDB2、KCTD12、PTPRB和CAV1。其生物学功能主要富集于信号传导等方面。其中,表达显著上调的基因有CAV1,显著下调的基因有GIMAP6、TGFBR2、LHFP和PTPRB(P<0.05)。LMO2与GIMAP6(r=0.51)、TGFBR2(r=0.46)、LHFP(r=0.52)、PTPRB(r=0.48)和CAV1(r=0.43)等关键基因的表达呈显著正相关。结论LMO2在乳腺癌组织中呈低表达,LMO2与GIMAP6、TGFBR2、CAV1等关键基因共同参与了乳腺癌发生相关的功能与通路。

Objective To investigate LMO2 expression and the biological functions of its co-expressed genes in breast cancer(BC).Methods LMO2 expression levels in various tumor types were extracted from the Oncomine database.Differences in LMO2 expression in BC tissues and normal breast tissues were analyzed using GEPIA,and the prognostic value of LMO2 expression in breast cancer was evaluated using KM plotter database.A co-expression gene network associated with LMO2 in BC was constructed using the Coexpedia database,and co-expressed genes that scored>3 were annotated using Funrich software.Hub genes with significant differential expression were identified using GEPIA.Correlations between LMO2 and hub genes,and the KEGG pathways associated with these genes were analyzed.Results LMO2 mRNA and protein expression levels were significantly lower in BC tissues than in normal tissues(P<0.05).Low LMO2 expression indicates a worse prognosis in patients with breast cancer.The main genes that co-expressed with LMO2 were ADGRL4,GIMAP6,PECAM1,TGFBR2,MEF2C,CD93,S1PR1,LHFP,GMFG,A2M,LDB2,KCTD12,PTPRB,and CAV1,whose biological functions were primarily enriched in signal transduction pathways.CAV1 was significantly up-regulated,and GIMAP6,TGFBR2,LHFP,and PTPRB were significantly down-regulated(P<0.05).LMO2 expression significantly correlated with that of GIMAP6(r=0.51),TGFBR2(r=0.46),LHFP(r=0.52),PTPRB(r=0.48),and CAV1(r=0.43).Conclusion LMO2 was significantly downregulated in BC,and was also involved in breast cancer-related functions and pathways in conjunction with GIMAP6,TGFBR2,CAV1,and other hub genes.