Oncogene-mediated metabolic gene signature predicts breast cancer outcome

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...

Full description

Saved in:
Bibliographic Details
Published in:NPJ breast cancer 2021-10, Vol.7 (1), p.141-13, Article 141
Main Authors: Aslan, Merve, Hsu, En-Chi, Garcia-Marques, Fernando J., Bermudez, Abel, Liu, Shiqin, Shen, Michelle, West, Meredith, Zhang, Chiyuan Amy, Rice, Meghan A., Brooks, James D., West, Robert, Pitteri, Sharon J., Győrffy, Balázs, Stoyanova, Tanya
Format: Article
Language:English
Subjects:
631/67/1347
692/53/2422
Biomedical and Life Sciences
Biomedicine
Breast cancer
Cancer Research
Cell Biology
Cell growth
Datasets
Gene expression
Glycoproteins
Human Genetics
Medical prognosis
Medical research
Metabolism
Oncology
Patients
Proteins
Tumors
Womens health
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2374-4677
2374-4677
DOI:10.1038/s41523-021-00341-6