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Identification of core genes for early diagnosis and the EMT modulation of ovarian serous cancer by bioinformatics perspective.

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.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7880353 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Identification of core genes for early diagnosis and the EMT modulation of ovarian serous cancer by bioinformatics perspective.

Zhang Yanna Y Wang Xun X Chen Xiancheng X

Aging 20210125 2

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 ...[more]

PMID: 33493131

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Project description:Ovarian cancer is a major cause of mortality in women. However, the molecular events underlying the pathogenesis of the disease are yet to be fully elucidated. In the present study, an integrated bioinformatics analysis was performed to identify core genes involved in serous epithelial ovarian cancer. A total of three expression datasets were downloaded from the Gene Expression Omnibus database, and included 46 serous epithelial ovarian cancer and 30 ovarian surface epithelium samples. The three datasets were merged, and batch normalization was performed. The normalized merged data were subsequently analyzed for differentially expressed genes (DEGs). In total, 2,212 DEGs were identified, including 1,300 upregulated and 912 downregulated genes. Gene Ontology analysis revealed that these DEGs were primarily involved in 'regulation of cell cycle', 'mitosis', 'DNA packaging' and 'nucleosome assembly'. The main cellular components included 'extracellular region part', 'chromosome', 'extracellular matrix' and 'condensed chromosome kinetochore', whereas the molecular functions included 'Calcium ion binding', 'polysaccharide binding', 'enzyme inhibitor activity', 'growth factor activity', 'cyclin-dependent protein kinase regulator activity', 'microtubule motor activity' and 'Wnt receptor activity'. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that these DEGs were predominantly involved in 'Wnt signaling pathway', 'pathways in cancer', 'PI3K-Akt signaling pathway', 'cell cycle', 'ECM-receptor interaction', 'p53 signaling pathway' and 'focal adhesion'. The 20 most significant DEGs were identified from the protein-protein interaction network, and Oncomine analysis of these core genes revealed that 13 were upregulated and two were downregulated in serous epithelial ovarian cancer. Survival analysis revealed that cyclin B1, polo like kinase 1, G protein subunit ? transducin 1 and G protein subunit ? 12 are key molecules that may be involved in the prognosis of serous epithelial ovarian cancer. These core genes may provide novel treatment targets, although their roles in the carcinogenesis and prognosis of serous epithelial ovarian cancer require further study.

Project description:Epithelial ovarian cancers (EOCs) are fatal and obstinate among gynecological malignancies in advanced stage or relapsed status, with serous carcinomas accounting for the vast majority. Unlike EOCs, borderline ovarian tumors (BOTs), including serous BOTs, maintain a semimalignant appearance. Using gene ontology (GO)-based integrative analysis, we analyzed gene set databases of serous BOTs and serous ovarian carcinomas for dysregulated GO terms and pathways and identified multiple differentially expressed genes (DEGs) in various aspects. The SRC (SRC proto-oncogene, non-receptor tyrosine kinase) gene and dysfunctional aryl hydrocarbon receptor (AHR) binding pathway consistently influenced progression-free survival and overall survival, and immunohistochemical staining revealed elevated expression of related biomarkers (SRC, ARNT, and TBP) in serous BOT and ovarian carcinoma samples. Epithelial-mesenchymal transition (EMT) is important during tumorigenesis, and we confirmed the SNAI2 (Snail family transcriptional repressor 2, SLUG) gene showing significantly high performance by immunohistochemistry. During serous ovarian tumor formation, activated AHR in the cytoplasm could cooperate with SRC, enter cell nuclei, bind to AHR nuclear translocator (ARNT) together with TATA-Box Binding Protein (TBP), and act on DNA to initiate AHR-responsive genes to cause tumor or cancer initiation. Additionally, SNAI2 in the tumor microenvironment can facilitate EMT accompanied by tumorigenesis. Although it has not been possible to classify serous BOTs and serous ovarian carcinomas as the same EOC subtype, the key determinants of relevant DEGs (SRC, ARNT, TBP, and SNAI2) found here had a crucial role in the pathogenetic mechanism of both tumor types, implying gradual evolutionary tendencies from serous BOTs to ovarian carcinomas. In the future, targeted therapy could focus on these revealed targets together with precise detection to improve therapeutic effects and patient survival rates.

Dataset Information

Identification of core genes for early diagnosis and the EMT modulation of ovarian serous cancer by bioinformatics perspective.

Publications

Identification of core genes for early diagnosis and the EMT modulation of ovarian serous cancer by bioinformatics perspective.

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