Research Paper Volume 12, Issue 21 pp 21874—21889
Integrated analysis of transcriptomic and metabolomic data demonstrates the significant role of pyruvate carboxylase in the progression of ovarian cancer
- 1 Department of Gynecology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
- 2 Department of Gynecology, Affiliated Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou 310006, Zhejiang Province, China
Received: April 3, 2020 Accepted: August 14, 2020 Published: November 7, 2020
https://doi.org/10.18632/aging.104004How to Cite
Copyright: © 2020 Shang 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
The aim of this study was to explore prognosis-related biomarkers and underlying mechanisms during ovarian carcinoma progression and development. mRNA expression profiles and 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.
Abbreviations
TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; PC: Pyruvate carboxylase; DEGs: Differentially expressed genes; shPC: PC-shRNA; EOC: Epithelial ovarian carcinomas; PPI: Protein-protein interaction; BCAAs: Branched-chain amino acids; T2D: Type 2 diabetes; FFAs: Free fatty acids; CPM: Count per million; KM: Kaplan-Meier; KEGG: Kyoto Encyclopedia of Genes and Genomes; DAVID: Database for Annotation, Visualization and Integrated Discovery; FBS: Fetal bovine serum; QC: Quality control; PCA: Principal component analysis; PLS-DA: Partial least squares discriminant analysis; FDR: False discovery rate; FPKM: Fragments Per Kilobase of Exon Per Million Fragments Mapped; GO: Gene ontology; GSEA: Gene set enrichment analysis; TF: Transcription factor; IDH: Isocitrate dehydrogenase.