Research Paper Volume 13, Issue 2 pp 3112—3145
Identification of core genes for early diagnosis and the EMT modulation of ovarian serous cancer by bioinformatics perspective
- 1 State Key Laboratory of Biotherapy, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, High Technological Development Zone, Chengdu 610041, Sichuan, People’s Republic of China
Received: August 28, 2020 Accepted: November 30, 2020 Published: January 25, 2021
https://doi.org/10.18632/aging.202524How to Cite
Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Ovarian serous carcinoma (OSC), as a common malignant tumor, poses a serious threat to women's health in that epithelial-mesenchymal transformation (EMT)-related modulation becomes heavily implicated in the invasion and progression of OSC. In this study, two core genes (BUB1B and NDC80) among the 16 hub genes have been identified to be involved in the molecular regulation of EMT and associated with the poor early survival of OSC at stages I+II. Through the Gene Regulatory Networks (GRN) analysis of 15 EMT regulators and core genes, it was revealed that TFAP2A and hsa-miR-655 could elaborately modulate EMT development of OSC. Next genetic variation analysis indicated that EMT regulator ELF3 would also serve as a crucial part in the occurrence and progression of OSC. Eventually, survival investigation suggested that TFAP2A, ELF3 and hsa-miR-655 were significantly associated with the overall survival of progressive OSC patients. Thus, combined with diversified bioinformatic analyses, BUB1B, NDC80, TFAP2A, ELF3 and hsa-miR-655 may act as the key biomarkers for early clinical diagnosis and prognosis evaluation of OSC patients as well as potential therapeutic target-points.
Abbreviations
OSC: ovarian serous cancer/carcinoma; EMT: epithelial-mesenchymal transformation; EOC: epithelial ovarian cancer; GEO: Gene Expression Omnibus; co-DEGs: common differential expression genes; PPIs: Protein-protein interactions; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Gene and Genome; GRN: Gene Regulatory Networks; TF: transcription factor; ELF3: E74 like ETS transcription factor 3; TFAP2A: transcription factor AP-2 alpha; BUB1B: BUB1 mitotic checkpoint serine/threonine kinase B; NDC80: NDC80 kinetochore complex component; CDH1/E-cadherin: cadherin 1; CDH2/N-cadherin: cadherin 2; ZEB1/2: zinc finger E-box binding homeobox 1/2; SNAI1/2: snail family transcriptional repressor 1/2; TWIST1/2: twist family bHLH transcription factor 1/2; AXL: AXL receptor tyrosine kinase; BIRC5: baculoviral IAP repeat containing 5; CTNNB1: catenin beta 1; PARP-1: poly(ADP-ribose) polymerase 1; ARK5/NUAK1: NUAK family kinase 1; HOXA10: homeobox A10.