Breast cancer remains the most common malignancy among women, with significant heterogeneity in molecular subtypes and clinical outcomes. This study examines the clinicopathological significance of GLUT-1, GLS1, and GLS2 expression in breast cancer tissues from Jordanian patients, focusing on their role in metabolic reprogramming and potential as therapeutic targets. Using tissue microarray analysis and immunohistochemistry, we evaluated 306 invasive breast cancer cases and 52 normal tissue samples. Overexpression of all three markers was observed in tumor tissues compared to normal samples (p ≤ .01). GLUT-1 and GLS2 showed significant associations with higher tumor grades and triple-negative breast cancer (TNBC) subtypes, highlighting their potential role in aggressive tumor biology. Conversely, GLS1 expression was consistently elevated in cancer tissues but did not vary significantly across grades or subtypes. Strong correlations between high GLUT-1/GLS2 expression and Ki-67 proliferative index underscore their contributions to tumor proliferation and metabolic adaptation. Population-specific patterns, such as the higher GLS2 expression in HER2-negative cases, reflect potential genetic or environmental influences unique to Jordanian patients. These findings emphasize the critical role of metabolic reprogramming in breast cancer progression and underscore the translational potential of targeting GLUT-1 and GLS2, particularly in aggressive subtypes like TNBC. Further research is warranted to explore functional mechanisms and validate these markers in diverse populations. This study provides novel insights into the metabolic dynamics of breast cancer, offering a foundation for regionally tailored therapeutic strategies.
Keywords: Breast cancer; GLUT-1; Glutaminases; Metabolic reprogramming; Triple-negative breast cancer.
© 2025. The Author(s).