Department of Endocrinology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Endocrinology and Metabolism, Huai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.
J Cell Physiol. 2018 Nov;233(11):8551-8557. doi: 10.1002/jcp.26440. Epub 2018 Jun 15.
Although diabetes mellitus (DM) is reported as an independent risk factor for colorectal cancer (CRC) in many researches, the underlying pathophysiology is still unclear. We investigated the differentially expressed genes (DEGs) for the diabetes and CRC to reveal the underlying pathophysiological association between the type 2-diabetic (T2D) and CRC. Gene expression profiles for T2D (GSE55650), CRC (GSE8671), and Metformin treated cell lines (GSE67342) were downloaded from GEO database. The DEGs between T2D samples and their control samples were identified with t-test and variance analysis. After cluster analysis and functional enrichment analysis, protein-protein interaction (PPI) network was constructed to find potential genes for diabetes and CRC in Metformin's treatment. Totally, we identified 583 overlapped genes, 169 common DEGs, and 414 independent DEGs between T2D and CRC samples. The common genes contained 89 up-regulated (DEGs1) and 80 down-regulated genes (DEGs3); and independent DEGs contained 270 down-regulated genes (DEGs4) in diabetes and 144 down-regulated genes (DEGs2) in CRC. In enrichment analysis, the Ribosome pathway was significantly enriched by the independent DEGs. The common genes were mainly enriched in some inflammatory related pathways. Two target genes of Metformin were significantly interacted with six hub genes (HADHB, NDUFS3, TAF1, MYC, HNFF4A, and MAX) with significant changes in expression values (P < 0.05, t-test). To summary, it is suggested that the six hub genes might play important roles in the process of Metformin treatment for diabetes and CRC. However, specific pathology remains to be further studied.
虽然糖尿病（DM）在许多研究中被报道为结直肠癌（CRC）的独立危险因素，但潜在的病理生理学机制仍不清楚。我们研究了糖尿病和 CRC 的差异表达基因（DEGs），以揭示 2 型糖尿病（T2D）和 CRC 之间潜在的病理生理学关联。从 GEO 数据库中下载了 T2D（GSE55650）、CRC（GSE8671）和二甲双胍处理细胞系（GSE67342）的基因表达谱。使用 t 检验和方差分析鉴定 T2D 样本与其对照样本之间的 DEGs。经过聚类分析和功能富集分析，构建蛋白质-蛋白质相互作用（PPI）网络，以寻找二甲双胍治疗中糖尿病和 CRC 的潜在基因。总共，我们鉴定了 583 个重叠基因、169 个共同 DEGs 和 T2D 和 CRC 样本之间的 414 个独立 DEGs。共同基因包含 89 个上调（DEGs1）和 80 个下调基因（DEGs3）；独立 DEGs 中糖尿病中有 270 个下调基因（DEGs4），CRC 中有 144 个下调基因（DEGs2）。在富集分析中，核糖体途径被独立的 DEGs 显著富集。共同基因主要富集在一些炎症相关途径中。二甲双胍的两个靶基因与六个表达值有显著变化的关键基因（HADHB、NDUFS3、TAF1、MYC、HNFF4A 和 MAX）显著相互作用（P<0.05，t 检验）。总结，建议这六个关键基因可能在二甲双胍治疗糖尿病和 CRC 的过程中发挥重要作用。然而，具体的病理仍有待进一步研究。
