Abstract 17P
Background
Breast cancer (BC) remains heterogeneous in terms of prognosis and response to treatment. Metabolic reprogramming is a critical part of oncogenesis and a potential therapeutic target. Glutaminase (GLS), which generates glutamate from glutamine, plays a role in TNBC. However, targeting GLS directly may be difficult, as it is essential for normal cell function. This study aimed to determine potential targets in BC associated with glutamine metabolism and evaluate their prognostic value in BC.
Methods
The iNET model (https://inetmodels.com) was used to identify genes in BC that directly interacted with GLS using RNA-sequencing data. The prognostic significance of Tripartite Motif Containing 2 (TRIM2) mRNA was assessed in BC transcriptomic data (n=16,575), and TRIM2 protein expression was evaluated using immunohistochemistry (n=749) in early-stage invasive breast cancer patients with long-term follow-up. The associations between TRIM2 expression and clinicopathological features and patient outcome were evaluated.
Results
Pathway analysis identified TRIM2 expression as an important gene co-expressed with high GLS expression in BC. High TRIM2 mRNA and TRIM2 protein expression were associated with TNBC (p<0.01). TRIM2 was a predictor of poor distant metastasis free survival (DMFS) in TNBC (p<0.01) which was independent of established prognostic factors (p<0.05) particularly in those who received chemotherapy (p<0.05). In addition, TRIM2 was a predictor of shorter DMFS in TNBC treated with chemotherapy (p<0.01).
Conclusions
This study provides evidence for association between TRIM2 and poor patient outcome in TNBC especially those treated with chemotherapy. However, the molecular mechanisms and functional behaviour of TRIM2 and the functional link with GLS in BC warrant further exploration using in vitro models.
Legal entity responsible for the study
The author.
Funding
University of Botswana PathLAKE Digital Pathology Consortium.
Disclosure
The author has declared no conflicts of interest.