Oncogene-mediated metabolic gene signature predicts breast cancer outcome.
Merve AslanEn-Chi HsuFernando Jose Garcia MarquesAbel BermudezShiqin LiuMichelle ShenMeredith WestChiyuan Amy ZhangMeghan A RiceJames D BrooksRobert WestSharon J PitteriBalázs GyőrffyTanya StoyanovaPublished in: NPJ breast cancer (2021)
Breast cancer remains the second most lethal cancer among women in the United States and triple-negative breast cancer is the most aggressive subtype with limited treatment options. Trop2, a cell membrane glycoprotein, is overexpressed in almost all epithelial cancers. In this study, we demonstrate that Trop2 is overexpressed in triple-negative breast cancer (TNBC), and downregulation of Trop2 delays TNBC cell and tumor growth supporting the oncogenic role of Trop2 in breast cancer. Through proteomic profiling, we discovered a metabolic signature comprised of TALDO1, GPI, LDHA, SHMT2, and ADK proteins that were downregulated in Trop2-depleted breast cancer tumors. The identified oncogene-mediated metabolic gene signature is significantly upregulated in TNBC patients across multiple RNA-expression clinical datasets. Our study further reveals that the metabolic gene signature reliably predicts poor survival of breast cancer patients with early stages of the disease. Taken together, our study identified a new five-gene metabolic signature as an accurate predictor of breast cancer outcome.
Keyphrases
- mass spectrometry
- high resolution
- copy number
- genome wide
- breast cancer risk
- end stage renal disease
- single cell
- poor prognosis
- stem cells
- metabolic syndrome
- transcription factor
- childhood cancer
- signaling pathway
- adipose tissue
- polycystic ovary syndrome
- mesenchymal stem cells
- young adults
- squamous cell carcinoma
- peritoneal dialysis
- long non coding rna
- nucleic acid