Integrated analysis of transcriptomic and metabolomic data demonstrates the significant role of pyruvate carboxylase in the progression of ovarian cancer

摘要

The aim of this study was to explore prognosis-related biomarkers and underlying mechanisms during ovarian carcinoma progression and development. mRNA expression profiles and {"type":"entrez-geo","attrs":{"text":"GSE49997","term_id":"49997"}}GSE49997 dataset were downloaded. Survival analyses were performed for genes with high expression levels. Expression level of candidate genes was explored in four ovarian cancer cells lines. Pyruvate carboxylase (PC) was found to be one of significantly differentially expressed gene (DEG). The role of PC knockdown was analyzed in SKOV cells using cell proliferation, flow cytometric, and Transwell migration and invasion assays. DEGs and metabolites in PC-shRNA (shPC)-treated samples vs. control groups were identified. PC was a prognosis-related gene and related to metabolic pathway. Knockdown of PC regulated cell proliferation, cell cycle progression, and migration and invasion of SKOV-3 cells. Transcriptome sequencing analyses showed STAT1 and TP53 gained higher degrees in PPI network. A total of 44 metabolites were identified. These DEGs and metabolites in PC samples were related with neuroactive ligands receptor interaction, glycine, serine and threonine metabolism, and ABC transporter pathways. PC may affect the tumor biology of ovarian cancer through the dysregulation of glycine, serine, and threonine metabolism, and ABC transporter pathways, as well as STAT1 and TP53 expression.