Background: In worldwide, colorectal cancer (CRC) is very common and the mechanisms remain unclear. This study aims to identify between adenomas with epithelial dislocation (false invasion) and adenomas with early adenocarcinoma (true invasion).
Methods: GSE41655 and GSE57965 datasets were obtained in the Gene Expression Omnibus (GEO) database. microRNA expression profiles and clinicopathological data from the TCGA (The Cancer Genome Atlas) database were downloaded to further validate the results in GEO. GEO software and the GEO2R calculation method were used to analyze two gene profiles. The co-expression of differentially expressed microRNAs (DEMs) and genes (DEGs) were identified and searched in the FunRich databases for pathway and ontology analysis. Cytoscape was utilized to construct the mRNA-microRNA network. Validation of gene expression levels was conducted by online databases and qRT-PCR and IHC experiments.
Results: In total, 6 DEMs and 34 DEGs are selected after calculating. KEGG results indicated that genes are enriched in certain tumor associated pathways. Four out of 6 microRNAs had a significant relationship with the overall survival (P < 0.05) and showed a good performance in predicting the survival risk of patients with colorectal carcinoma. Furthermore, expression levels of hsa-miR-455 and hsa-miR-125a were then verified by qRT-PCR which all target BCL2L12. IHC results showed that the expression level of BCL2L12 was higher in adenocarcinoma than in adenoma. Based on the selected gene, the top 10 small molecules were screened out as potential drugs.
Conclusion: By using microarray and bioinformatics analyses, DEMs and DEGs were selected and a complete gene network was constructed. To our knowledge, BCL2L12 and related molecules including hsa-miR-455 and hsa-miR-125a were firstly identified as potential biomarkers in the progression from adenoma to adenocarcinoma.



中文翻译：

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使用生物信息学分析鉴定腺瘤和腺癌之间的 microRNA 特征和关键基因

背景：在世界范围内，结直肠癌 (CRC) 非常常见，其机制仍不清楚。本研究旨在鉴别上皮脱位（假浸润）的腺瘤和早期腺癌（真浸润）的腺瘤。
方法：GSE41655 和 GSE57965 数据集在 Gene Expression Omnibus (GEO) 数据库中获得。下载了来自 TCGA（癌症基因组图谱）数据库的 microRNA 表达谱和临床病理学数据，以进一步验证 GEO 中的结果。GEO软件和GEO2R计算方法用于分析两个基因谱。在 FunRich 数据库中识别和搜索了差异表达的 microRNA (DEM) 和基因 (DEG) 的共表达，以进行通路和本体分析。Cytoscape 用于构建 mRNA-microRNA 网络。基因表达水平的验证通过在线数据库和 qRT-PCR 和 IHC 实验进行。
结果：经过计算，总共选择了 6 个 DEM 和 34 个 DEG。KEGG 结果表明基因在某些肿瘤相关通路中富集。6个microRNA中有4个与总生存期有显着关系（P < 0.05），在预测结直肠癌患者的生存风险方面表现出良好的表现。此外，然后通过全部靶向 BCL2L12 的 qRT-PCR 验证 hsa-miR-455 和 hsa-miR-125a 的表达水平。IHC结果显示BCL2L12在腺癌中的表达水平高于腺瘤。根据选择的基因，筛选出前10个小分子作为潜在药物。
结论：通过使用微阵列和生物信息学分析，选择了 DEM 和 DEG，并构建了完整的基因网络。据我们所知，BCL2L12 和包括 hsa-miR-455 和 hsa-miR-125a 在内的相关分子首先被确定为从腺瘤发展为腺癌的潜在生物标志物。