基于多组学数据分析宫颈癌关键新靶标基因的探索

Exploration of Key New Target Genes for Cervical Cancer Based on Multiomic Data Analysis

目的识别宫颈癌进展不同阶段的关键基因,为寻找治疗靶点提供数据支持。方法采用GEO数据库中GSE9750、GSE63514、GSE7803数据和TCGA数据进行差异表达基因计算和验证。利用韦恩分析择选不同进展阶段的关键基因。使用TIMER2.0数据库评价免疫细胞浸润情况。结果AURKA和CDKN2A属于过表达基因,在宫颈癌进展全程中起着重要作用,高表达组患者总生存率均低于低表达组,差异具有显著性,P<0.05。独立存在于CIN1阶段的基因与不良预后无关。AURKA与巨噬细胞(r=0.172,P<0.05)呈正相关,与B细胞(r=-0.167,P<0.05)、树突细胞(r=-0.124,P<0.05)和肥大细胞(r=-0.122,P<0.05)呈负相关。CDKN2A与CD8+T细胞呈正相关(r=0.127,P<0.05),与嗜中性粒细胞呈负相关(r=-0.123,P<0.05)。KEGG分析显示,CIN1阶段主要信号通路是hsa04110细胞周期;HISL和肿瘤阶段主要信号通路是hsa05200癌症通路。结论选取不同平台的宫颈癌数据,确定了在宫颈癌演变的不同阶段中与不良预后相关的关键基因是AURKA和CDKN2A,为治疗提供新的分子靶点。

Objective To identify key genes in different stages of cervical cancer progression and provide data support for the search for therapeutic targets.Methods GSE9750,GSE63514,GSE7803 and TCGA data in GEO database were used to calculate and verify differentially expressed genes.Key genes at different stages of progression were selected using Wayne analysis.The infiltration of immune cells was evaluated using TIMER2.0 database.Results AURKA and CDKN2A are overexpressed genes,which play an important role in the progression of cervical cancer.The overall survival rate of patients in the high expression group was lower than that in the low expression group,and the difference was significant(P<0.05).Genes present independently at CIN1 stage were not associated with poor prognosis.AURKA was positively correlated with macrophages(r=0.172,P<0.05)and negatively correlated with B cells(r=-0.167,P<0.05),dendritic cells(r=-0.124,P<0.05)and mast cells(r=-0.122,P<0.05).CDKN2A was positively correlated with CD8+T cells(r=0.127,P<0.05),and negatively correlated with neutrophils(r=-0.123,P<0.05).KEGG analysis showed that the main signaling pathway of CIN1 phase was hsa04110 cell cycle.HISL and the main signaling pathway of tumor stage is hsa05200 cancer pathway.Conclusion Cervical cancer data from different platforms were selected to identify the key genes associated with poor prognosis in different stages of cervical cancer evolution as AURKA and CDKN2A,providing new molecular targets for treatment.