Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China.
Cancer Research Institute, Central South University, Changsha, P.R. China.
Int J Med Sci. 2019 Jun 2;16(6):800-812. doi: 10.7150/ijms.34172. eCollection 2019.
Cervical cancer is a common malignant tumour of the female reproductive system that seriously threatens the health of women. The aims of this study were to identify key genes and pathways and to illuminate new molecular mechanisms underlying cervical cancer. Altogether, 1829 DEGs were identified, including 794 significantly down-regulated DEGs and 1035 significantly up-regulated DEGs. GO analysis suggested that the up-regulated DEGs were mainly enriched in mitotic cell cycle processes, including DNA replication, organelle fission, chromosome segregation and cell cycle phase transition, and that the down-regulated DEGs were primarily enriched in development and differentiation processes, such as tissue development, epidermis development, skin development, keratinocyte differentiation, epidermal cell differentiation and epithelial cell differentiation. KEGG pathway analysis showed that the DEGs were significantly enriched in cell cycle, DNA replication, the p53 signalling pathway, pathways in cancer and oocyte meiosis. The top 9 hub genes with a high degree of connectivity (over 72 in the PPI network) were down-regulated TSPO, CCND1, and FOS and up-regulated CDK1, TOP2A, CCNB1, PCNA, BIRC5 and MAD2L1. Module analysis indicated that the top 3 modules were significantly enriched in mitotic cell cycle, DNA replication and regulation of cell cycle ( < 0.01). The heat map based on TCGA database preliminarily demonstrated the expression change of the key genes in cervical cancer. GSEA results were basically coincident with the front enrichment analysis results. By comprehensive analysis, we confirmed that cell cycle was a key biological process and a critical driver in cervical cancer. In conclusion, this study identified DEGs and screened the key genes and pathways closely related to cervical cancer by bioinformatics analysis, simultaneously deepening our understanding of the molecular mechanisms underlying the occurrence and progression of cervical cancer. These results might hold promise for finding potential therapeutic targets of cervical cancer.
宫颈癌是一种常见的女性生殖系统恶性肿瘤，严重威胁着女性的健康。本研究旨在鉴定关键基因和通路，阐明宫颈癌发生的新分子机制。共鉴定到 1829 个差异表达基因，包括 794 个显著下调的差异表达基因和 1035 个显著上调的差异表达基因。GO 分析表明，上调的差异表达基因主要富集在有丝分裂细胞周期过程中，包括 DNA 复制、细胞器分裂、染色体分离和细胞周期相变，而下调的差异表达基因主要富集在发育和分化过程中，如组织发育、表皮发育、皮肤发育、角蛋白细胞分化、表皮细胞分化和上皮细胞分化。KEGG 通路分析表明，差异表达基因在细胞周期、DNA 复制、p53 信号通路、癌症通路和卵母细胞减数分裂中显著富集。具有高连接度（PPI 网络中超过 72 个）的前 9 个枢纽基因下调 TSPO、CCND1 和 FOS，上调 CDK1、TOP2A、CCNB1、PCNA、BIRC5 和 MAD2L1。模块分析表明，前 3 个模块在有丝分裂细胞周期、DNA 复制和细胞周期调控中显著富集（<0.01）。基于 TCGA 数据库的热图初步表明了关键基因在宫颈癌中的表达变化。GSEA 结果与前富集分析结果基本一致。通过综合分析，我们证实细胞周期是宫颈癌的关键生物学过程和关键驱动因素。总之，本研究通过生物信息学分析鉴定了差异表达基因，并筛选出与宫颈癌密切相关的关键基因和通路，同时加深了我们对宫颈癌发生和发展分子机制的理解。这些结果可能为寻找宫颈癌潜在的治疗靶点提供了希望。
