基于随机森林算法的宫颈癌淋巴结转移相关基因的生物信息学筛选

摘要

Objective To screen the genes most relevant to lymph node metastasis of cervical cancer and identify the genes at the key knots of the regulatory network to provide the potential targets for cervical cancer intervention.Methods The transcriptional profiling database of TCGA was used, and random forests algorithm was adopted to rank the genes related to lymph node metastasis extracted from GeneCards database.STRING and Cytospace tolls were used to build the interactive regulatory network and identify the most weighted genes localized in the central of the network.DAVID platform was used to perform a functional annotation for the whole geneset.Results We ranked 2784 genes in respect to their potential contributions to lymph node metastasis of cervical cancer and identified the genes at the key knob.The genes related to cancer metastasis were enriched to cytokines pathway, MAPK pathway, wnt pathway, intercellular interaction, adhesive conjunction, cellular skeleton regulation, etc.Some of the identified key genes, like EGFR, NOTCH1, RHOA, etc. have been verified to be closely related cervical cancer metastasis in the basic and clinical research. Conclusion Random forests algorithm is useful, taking advantages of TCGA database, in enriching the genes playing significant role in cervical cancer metastasis.A majority of the genes in the analyzed geneset were indicated to be significantly correlated with lymph node metastasis.%目的：分析与淋巴结转移最相关的基因集和基因集中的关键节点性基因，为宫颈癌淋巴结转移预测潜在干预靶点。方法利用TCGA宫颈癌患者转录组数据集，使用随机森林算法对淋巴结转移最相关基因进行分析和排名，使用STRING和Cytospace对这些相关基因进行互作网络分析，筛选对其他基因具有最广泛相互作用的基因节点，使用DAVID对这些基因在整体上进行功能识别。结果获得淋巴结转移相关基因重要性排序（2784个），并获得其中的关键节点基因（前13位分别为EGFR，NOTCH1，RHOA），这些基因均与淋巴结转移显著相关（ P＜0．05）。与淋巴结转移最相关的基因主要聚集在趋化因子信号通路、MAPK通路、细胞间相互作用、黏着连接、细胞骨架调控、wnt通路等。对这些有意义的宫颈癌转移相关基因集在统计学上进行了验证，获得的关键节点基因如EGFR，NOTCH1，RHOA在临床水平均已发现与宫颈癌淋巴结转移显著相关。结论随机森林算法是一个有效的方法，采用此方法获得的宫颈癌转移相关的基因集有很大比例与淋巴结转移显著相关。