从肝癌基因突变信息寻找新的药物治疗适应证
Discovery of new drug therapeutic indications from gene mutation information for hepatocellular carcinoma
摘要：
肝细胞癌（HCC）是最常见的原发性肝脏恶性肿瘤，是全球癌症相关死亡的主要原因。然而，目前使用的疗法不可能治愈，尽管有许多尝试和临床试验，但没有这么多批准的HCC靶向治疗。因此，有必要确定其他治疗策略来阻断HCC肿瘤的生长。作为一种癌症疾病，它与异常的基因组和转录景观有关。我们试图使用一种系统的药物重新定位生物信息学方法来识别治疗HCC的新候选药物，该方法不仅考虑了异常的基因组信息，还考虑了转录景观的变化。首先，我们根据人类突变数据筛选在大多数HCC样本中频繁突变的HCC特征基因的集合。然后，结合TCGA中HCC的基因表达数据，对HCC的核心基因进行分类。最后，基于kolmogorov-smirnov统计方法计算每种药物的治疗评分（TS）。利用这一策略，我们确定了五种与HCC相关的药物，包括三种治疗HCC的药物和两种可能对HCC有副作用的药物。此外，我们还对药物靶点进行了连接图（CMap）图谱相似性分析和KEGG富集分析。所有这些结果表明，我们的方法是有效的，准确地发现新的治疗方案，肝癌，并容易扩展到其他肿瘤。
英文摘要：
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. However, cure is not possible with currently used therapies, and there is not so much approved targeted therapy for HCC despite numerous attempts and clinical trials. So, it is essential to identify additional therapeutic strategies to block the growth of HCC tumors. As a cancer disease, it is associated with aberrant genomic and transcriptional landscapes. We sought to use a systematic drug repositioning bioinformatics approach to identify novel candidate drugs to treat HCC, which considers not only aberrant genomic information, but also the changes of transcriptional landscapes. First, we screen the collection of HCC feature genes that frequently mutated in most samples of HCC based on human mutation data. Then, the gene expression data of HCC in TCGA are combined to classify the kernel genes of HCC. Finally, the therapeutic score (TS) of each drug is calculated based on the kolmogorov-smirnov statistical method. Using this strategy, we identified five drugs that associated with HCC, including three drugs that could treat HCC and two drugs that might have side-effect on HCC. In addition, we also make Connectivity Map (CMap) profiles similarity analysis and KEGG enrichment analysis on drug targets. All these findings suggest that our approach is effective for accurate discovering novel therapeutic options for HCC and easily to be extended to other tumors.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
