UGT2A3差异表达在结直肠癌发生和早期诊断中的作用机制

Mechanism of UGT2A3 differentially expression in the occurrence and early diagnosis of colorectal cancer

目的研究UDP-葡萄糖醛酸糖基转移酶(UGT)家族成员UGT2A3的差异表达在结直肠癌(CRC)发生中的作用及调控机制。方法从高通量基因表达(GEO)数据库和癌症基因组图集(TCGA)中共下载了9个CRC数据集。采用R语言分析UGT2A3在CRC组织和癌旁正常组织中的差异表达情况。在TCGA中根据UGT2A3的表达水平,在所有样本、正常组织、癌组织样本中分别选取表达最高和最低的前20例样本,比较免疫细胞丰度和免疫富集评分;筛选差异表达基因和差异表达miRNA,并进行差异表达基因的通路富集分析。结果UGT2A3在所有9个数据集的CRC组织中均明显下调。与UGT2A3高表达组相比,UGT2A3低表达组的ImmuneScore、EstimateScore和StromalScore得分明显较高,且免疫细胞丰度较高(记忆B细胞除外)。在正常组织中,UGT2A3的差异表达主要影响癌症相关通路,而在CRC组织中主要影响代谢途径。miR-194-2、miR-224和miR-551b在所有分组中均显著差异表达,其被认为是CRC中潜在的UGT2A3上游调控基因。结论UGT2A3、miR-194-2、miR-224和miR-551b可作为CRC潜在的诊断生物标志物。

Objective To investigate the role and regulatory mechanism of UGT2A3 differential expression in colorectal carcinogenesis.Methods Nine CRC datasets were downloaded from GEO database and TCGA.R language was used to analyze the differential expression of UGT2A3 in cancer and normal tissues.According to the expression level of UGT2A3 in TCGA,the top 20 samples with the highest expression and the lowest expression were selected from normal tissues and CRC tissues,respectively.The abundance of immune cells and immune enrichment score were compared,the differentially expressed genes and differentially expressed miRNAs were screened,and the pathway enrichment analysis of differentially expressed genes was performed.Results UGT2A3 was down regulated in all 9 CRC datasets.In all sample types,compared with the UGT2A3 high expression group,the UGT2A3 low expression group had significantly higher ImmuneScore,EstimateScoreandStromalScore,and had higher abundance of immune cells(except memory B cells).In normal tissues,the differential expression of UGT2A3 mainly affects cancer-related pathways,while in tumor tissues,it mainly affects metabolic pathways.miR-194-2,miR-224 and miR-551b were differentially expressed in all groups,which were considered as potential UGT2A3 upstream regulatory genes in CRC.Conclusions UGT2A3,miR-194-2,miR-224 and miR-551b can be used as potential biomarkers for the diagnosis of CRC.