Reference Module-Based Analysis of Ovarian Cancer Transcriptome Identifies Important Modules and Potential Drugs

• Published in: Biochemical genetics 2022-02, Vol.60 (1), p.433-451
• Main Authors: Lai, Xuedan, Lin, Peihong, Ye, Jianwen, Liu, Wei, Lin, Shiqiang, Lin, Zhou
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cancer; Datasets; DNA microarrays; Drug development; Drugs; Epithelium; Gene expression; Gene Expression Profiling; Gene Regulatory Networks; Genes; Health services; Human Genetics; Humans; Medical Microbiology; Medical prognosis; Mesenchyme; Methodology Article; Modules; Network analysis; Ovarian cancer; Ovarian Neoplasms - genetics; Patients; Pharmaceutical Preparations; Pluripotency; Prognosis; Single-nucleotide polymorphism; Stability analysis; Stroma; Transcriptome; Transcriptomes; Zoology
• ISSN: 0006-2928; 1573-4927
• DOI: 10.1007/s10528-021-10101-7

Ovarian cancer (OVC) is often diagnosed at the advanced stage resulting in a poor overall outcome for the patient. The disease mechanisms, prognosis, and treatment require imperative elucidation. A rank-based module-centric framework was proposed to analyze the key modules related to the development, prognosis, and treatment of OVC. The ovarian cancer cell line microarray dataset GSE43765 from the Gene Expression Omnibus database was used to construct the reference modules by weighted gene correlation network analysis. Twenty-three reference modules were tested for stability and functionally annotated. Furthermore, to demonstrate the utility of reference modules, two more OVC datasets were collected, and their gene expression profiles were projected to the reference modules to generate a module-level expression. An epithelial-mesenchymal transition module was activated in OVC compared to the normal epithelium, and a pluripotency module was activated in ovarian cancer stroma compared to ovarian cancer epithelium. Seven differentially expressed modules were identified in OVC compared to the normal ovarian epithelium, with five up-regulated, and two down-regulated. One module was identified to be predictive of patient overall survival. Four modules were enriched with SNP signals. Based on differentially expressed modules and hub genes, five candidate drugs were screened. The hub genes of those modules merit further investigation. We firstly propose the reference module-based analysis of OVC. The utility of the analysis framework can be extended to transcriptome data of other kinds of diseases.