运用生物信息学方法分析RAS通路中相关基因与宫颈癌转移之间关系的研究

Analysis of relationship between RAS pathway related genes and cervical cancer metastasis using bioinformatics methods

目的探究与宫颈癌发展密切相关的信号通路关键分子,运用生物信息学方法来分析RAS蛋白信号通路与宫颈癌转移之间关系。方法分析受miR-3162-5p调控的信号通路,选出与宫颈癌发展相关的高分通路,运用Oncomine检索通路中的基因在宫颈癌中的表达情况,筛选出差异表达基因,利用STRING和Cytoscape构建了蛋白质-蛋白质相互作用网络(PPI)和模块分析。结果本研究运用生物信息学方法共筛选出了77个差异表达基因,包括31个高表达基因、42个低表达基因和4个有不同表达趋势的基因。从其中鉴定出24个关键基因,生存分析表明,非受体蛋白酪氨酸磷酸酶11型(PTPN11)、血管内皮生长因子A(VEGFA)、胰岛素样生长因子1(IGF1)、成纤维细胞生长因子受体2(FGFR2)、G蛋白亚单位γ7(GNG7)和原癌基因KIT配体(KITLG)可能参与宫颈癌的发生发展、侵袭或复发。免疫组织化学结果提示PTPN11在宫颈癌组织和宫颈非癌上皮中表达差异,差异具有统计学意义(P<0.05)。结论本研究中发现的差异基因和关键基因有助于了解宫颈癌发生和发展的分子机制,并为宫颈癌的诊断和治疗提供候选靶点。

Objective To analyze the relationship between the Ras signaling pathway and cervical cancer metastasis using bioinformatics methods,in order to explore the key molecules of signal pathways closely related to the development of cervical cancer.Methods The signaling pathways regulated by miR-3162-5p were analyzed and high-scoring pathways related to the development of cervical cancer were selected.Oncomine was used to retrieve the expression of genes in the pathway in cervical cancer,and the differentially expressed genes were screened out.Protein-protein interaction network(PPI)and module analysis were constructed using STRING and Cytoscape.Results A total of 77 differentially expressed genes were screened by bioinformatics methods,including 31 highly expressed genes,42 lowly expressed genes,and 4 genes with different expression trends.Among them,24 key genes were identified.Survival analysis showed that protein tyrosine phosphatase non-receptor type 11(PTPN11),vascular endothelial growth factor A(VEGFA),insulin like growth factor 1(IGF1),fibroblast growth factor receptor 2(FGFR2),G protein subunit gamma 7(GNG7),and KIT ligand(KITLG)may be involved in the occurrence,development,invasion,and recurrence of cervical cancer.The results of immunohistochemistry suggested that PTPN11 was expressed differentially between cervical cancer tissue and cervical non-cancerous epithelium,and the difference was statistically significant(P<0.05).Conclusion The differential genes and key genes identified in this study are helpful to understand the molecular mechanism of cervical cancer occurrence and development,and provide candidate targets for the diagnosis and treatment of this malignancy.