| Summary: | The reprogramming of energy metabolism is one of the hallmarks of cancer and is crucial for tumor progression. Altered aerobic glycolysis is a well-known characteristic of cancer cell metabolism. In the present study, the expression profiles of key metabolic genes (<i>HK2</i>, <i>PFKM,</i> and <i>PKM2</i>) were assessed in the breast cancer cohort of Pakistan using quantitative polymerase chain reaction (qPCR) and IHC. Expression patterns were correlated with molecular subtypes and clinical parameters in the patients. A significant upregulation of key glycolytic genes was observed in tumor samples in comparison to their adjacent controls (<i>p</i> < 0.0001). The expression of the studied glycolytic genes was significantly increased in late clinical stages, positive nodal involvement, and distant metastasis (<i>p</i> < 0.05). <i>HK2</i> and <i>PKM2</i> were found to be upregulated in luminal B, whereas <i>PFKM</i> was overexpressed in the luminal A subtype of breast cancer. The genes were positively correlated with the proliferation marker <i>Ki67</i> (<i>p</i> < 0.001). Moreover, moderate positive linear correlations between <i>HK2</i> and <i>PKM2</i> (r = 0.476), <i>HK2</i> and <i>PFKM</i> (r = 0.473), and <i>PKM2</i> and <i>PFKM</i> (r = 0.501) were also observed (<i>p</i> < 0.01). These findings validate that the key regulatory genes in glycolysis can serve as potential biomarkers and/or molecular targets for breast cancer management. However, the clinical significance of these molecules needs to be further validated through in vitro and in vivo experiments.
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