Background: Drug repurposing is a strategy that complements the conventional approach of developing new drugs. Hepatocellular carcinoma (HCC) is a highly prevalent type of liver cancer, necessitating an in-depth understanding of the underlying molecular alterations for improved treatment.Methods: We searched for a vast array of microarray experiments in addition to RNA-seq data. Through rigorous filtering processes, we have identified highly representative differentially expressed genes (DEGs) between tumor and non-tumor liver tissues and identified a distinct class of possible new candidate drugs.Results: Functional enrichment analysis revealed distinct biological processes associated with metal ions, including zinc, cadmium, and copper, potentially implicating chronic metal ion exposure in tumorigenesis. Conversely, up-regulated genes are associated with mitotic events and kinase activities, aligning with the relevance of kinases in HCC. To unravel the regulatory networks governing these DEGs, we employed topological analysis methods, identifying 25 hub genes and their regulatory transcription factors. In the pursuit of potential therapeutic options, we explored drug repurposing strategies based on computational approaches, analyzing their potential to reverse the expression patterns of key genes, including AURKA, CCNB1, CDK1, RRM2, and TOP2A. Potential therapeutic chemicals are alvocidib, AT-7519, kenpaullone, PHA-793887, JNJ-7706621, danusertibe, doxorubicin and analogues, mitoxantrone, podofilox, teniposide, and amonafide.Conclusion: This multi-omic study offers a comprehensive view of DEGs in HCC, shedding light on potential therapeutic targets and drug repurposing opportunities.
背景：药物再利用是一种补充传统新药开发策略的方法。肝细胞癌（HCC）作为高发性肝癌类型，亟需深入理解其潜在分子改变以优化治疗策略。 方法：本研究系统检索了大规模微阵列实验数据及RNA-seq数据。通过严格筛选流程，我们鉴定了肿瘤与非肿瘤肝组织间具有高度代表性的差异表达基因（DEGs），并识别出一类潜在的新型候选药物。 结果：功能富集分析揭示了与锌、镉、铜等金属离子相关的独特生物学过程，提示慢性金属离子暴露可能参与肿瘤发生机制。而上调基因则与有丝分裂事件及激酶活性密切相关，这与激酶在HCC中的关键作用相吻合。为解析调控这些DEGs的分子网络，我们采用拓扑分析方法鉴定出25个枢纽基因及其调控转录因子。在探索潜在治疗选择过程中，我们基于计算方法开展药物再利用策略研究，重点分析候选药物逆转AURKA、CCNB1、CDK1、RRM2和TOP2A等关键基因表达模式的潜力。潜在治疗化合物包括：阿伏西迪、AT-7519、肯帕罗酮、PHA-793887、JNJ-7706621、达努塞替、多柔比星及其类似物、米托蒽醌、鬼臼毒素、替尼泊苷及阿莫纳菲。 结论：本多组学研究为HCC差异表达基因提供了全景视角，不仅揭示了潜在治疗靶点，更为药物再利用策略开辟了新途径。
肿瘤(癌症)患者之家