Wang Lingxiang, Sun Tao, Li Shumei, Zhang Zhengmao, Jia Jingde, Shan Baoen
Department of Gynecology, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, 12 Jiankang Road, Shijiazhuang, Hebei 050011, China; Cancer Institute, Hebei Medical University Fourth Affiliated Hospital and Hebei Provincial Tumor Hospital, 12 Jiankang Road, Shijiazhuang, Hebei 050011, China.
Department of Orthopaedic Surgery, Hebei Medical University Third Affiliated Hospital, 139 Ziqiang Road, Shijiazhuang, Hebei 050051, China.
Transl Oncol. 2021 Jan;14(1):100885. doi: 10.1016/j.tranon.2020.100885. Epub 2020 Oct 9.
This study aimed to identify the biological processes associated with long-term survival in high-grade serous ovarian cancer (HGSOC). HGSOC cases obtained from The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) database were divided into long-term survivors (LTS) and normal-term survivors (NTS) based on survival cutoffs defined by the HGSOC cohort in the SEER database. Differentially expressed genes (DEGs) were screened using the generalized linear modeling (GLM) method. Gene Ontology (GO) functional and KEGG pathway enrichment analyses were performed using DAVID Bioinformatics Resources. DEG-related protein-protein interactions (PPI) were extracted from the STRING database and hub genes were identified using CytoHubba in the Cytoscape program. In total, 157 DEGs, including 155 upregulated and 2 downregulated genes, were identified. Upregulated genes were statistically enriched in 80 GO terms and 11 KEGG pathways related to energy and substrate metabolism, such as protein absorption, digestion, and metabolism as well as signaling pathways, including chromatin silencing, regulation of ERK1 and ERK2 cascade, and regulation of MAPKKK. ALB and POMC were the common hub genes. These findings reveal that protein anabolism is crucial to long-term survival, regulated by activation of the MAPK/ERK signaling pathway and chromatin silencing. Comprehensive understanding of the molecular mechanisms via further exploration may contribute toward an effective treatment for ovarian cancer.
本研究旨在确定与高级别浆液性卵巢癌（HGSOC）长期生存相关的生物学过程。从癌症基因组图谱卵巢癌（TCGA-OV）数据库中获取的HGSOC病例，根据SEER数据库中HGSOC队列定义的生存临界值，分为长期存活者（LTS）和正常期限存活者（NTS）。使用广义线性模型（GLM）方法筛选差异表达基因（DEG）。使用DAVID生物信息学资源进行基因本体论（GO）功能和KEGG通路富集分析。从STRING数据库中提取与DEG相关的蛋白质-蛋白质相互作用（PPI），并在Cytoscape程序中使用CytoHubba鉴定枢纽基因。总共鉴定出157个DEG，包括155个上调基因和2个下调基因。上调基因在80个GO术语和11条与能量和底物代谢相关的KEGG通路中具有统计学意义的富集，如蛋白质吸收、消化和代谢以及信号通路，包括染色质沉默、ERK1和ERK2级联反应的调节以及MAPKKK的调节。ALB和POMC是常见的枢纽基因。这些发现表明，蛋白质合成代谢对长期生存至关重要，受MAPK/ERK信号通路激活和染色质沉默的调节。通过进一步探索全面了解分子机制可能有助于卵巢癌的有效治疗。
