宫颈癌发病机制的探讨

Discussion of mechanism of cervical cancer

目的:探索宫颈癌发病的潜在机制,并筛选预测其发病风险的生物学标记物,为宫颈癌的防治提供理论依据。方法:采用基因集富集分析方法对NCBI GEO数据库中21例宫颈浸润性鳞状细胞癌标本和10例正常宫颈上皮标本的表达谱进行比较研究,分析其在信号通路中的富集特征与核心富集基因。利用功能方面的基因本体学和结构方面的染色体位置相关的基因集富集分析,进一步探讨宫颈癌的特征。结果:宫颈癌在DNA损伤修复和细胞周期调控相关通路中出现显著富集特征。其中最显著富集的是ATM信号通路(P<0.001),核心富集基因包括MRE11A、CDC25A、BLM、SMC1A、MDC1、H2AFX和BRCA1等。在生物学功能上出现内切酶活性相关基因集的显著富集(P=0.002)。差异性基因主要定位在染色体3q27区域(P=0.007)。结论:宫颈癌发病机制与DNA损伤修复和细胞周期调控密切相关,这些通路和相关基因有望成为预测宫颈癌发病风险的生物学标记物。

Objective： To explore the potential mechanism of cervical cancer, screen the biomarkers predicting its risk, provide a theoretical basis for prevention and treatment of cervical cancer. Methods： Gene set enrichment analysis was used to compare and research the expression spectrums of 21 cases with cervical invasive squamous cell carcinoma and 10 eases with normal cervical epithelium in NCBI GEO database, the enrichment characteristics and core enrichment genes in signal pathway were analyzed. The characteristics of cervical cancer were analyzed by gene ontology analysis of functional aspects and chromosomal location - associated gene set enrichment analysis of structural aspects. Results ： Significant enrichment characteristics were found in DNA damage repair and cell cycle regulation - related path- ways in cases with cervical cancer, enrichment of ATM signal pathway was significant （P 〈 0. 001 ） . Core enrichment genes included MREllA, CDC25A, BLM, SMC1A, MDC1, H2AFX and BRCA1, endonuclease activity was significantly enriched （P=0. 002） . Chro- mosome 3q27 region was prone to enrich overexpressed genes （P = 0. 007） . Conclusion： Cervical cancer is closely related to DNA damage repair and cell cycle regulation, these pathways and related genes are expected to be predictive biomarkers of cervical cancer.