Table_2_Integrated Analysis of Distant Metastasis-Associated Genes and Potential Drugs in Colon Adenocarcinoma.DOC

Background: Most colon adenocarcinoma (COAD) patients die of distant metastasis, though there are some therapies for metastatic COAD. However, the genes exclusively expressed in metastatic COAD remain unclear. This study aims to identify prognosis-related genes associated with distant metastasis and develop therapeutic strategies for COAD patients.Methods: Transcriptomic data from The Cancer Genome Atlas (TCGA; n = 514) cohort were analyzed as a discovery dataset. Next, the data from the GEPIA database and PROGgeneV2 database were used to validate our analysis. Key genes were identified based on the differential miRNA and mRNA expression with respect to M stage. The potential drugs targeting candidate differentially expressed genes (DEGs) were also investigated.Results: A total of 127 significantly DEGs in patients with distant metastasis compared with patients without distant metastasis were identified. Then, four prognosis-related genes (LEP, DLX2, CLSTN2, and REG3A) were selected based on clustering analysis and survival analysis. Finally, three compounds targeting the candidate DEGs, including ajmaline, TTNPB, and dydrogesterone, were predicted to be potential drugs for COAD.Conclusions: This study revealed that distant metastasis in COAD is associated with a specific group of genes, and three existing drugs may suppress the distant metastasis of COAD.

背景：大多数结肠腺癌（COAD）患者因远处转移而死亡，尽管对于转移性COAD存在某些治疗方法。然而，在转移性COAD中特异性表达的基因尚不明确。本研究旨在鉴定与远处转移相关的预后基因，并开发针对COAD患者的治疗策略。方法：以癌症基因组图谱（TCGA；n = 514）队列的转录组数据作为发现数据集进行分析。随后，利用GEPIA数据库和PROGgeneV2数据库的数据来验证我们的分析。基于M期相关的差异miRNA和mRNA表达，确定了关键基因。同时，还研究了针对候选差异表达基因（DEGs）的潜在药物。结果：在具有远处转移的患者与无远处转移的患者中，共鉴定出127个显著差异表达的DEGs。然后，基于聚类分析和生存分析，选取了四个与预后相关的基因（LEP、DLX2、CLSTN2和REG3A）。最终，预测了三种针对候选DEGs的化合物，包括阿莫林、TTNPB和炔孕酮，它们可能成为COAD的潜在药物。结论：本研究揭示了COAD的远处转移与特定基因群相关，三种现有药物可能抑制COAD的远处转移。