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 (HK2, PFKM, and PKM2) 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 (p < 0.0001). The expression of the studied glycolytic genes was significantly increased in late clinical stages, positive nodal involvement, and distant metastasis (p < 0.05). HK2 and PKM2 were found to be upregulated in luminal B, whereas PFKM was overexpressed in the luminal A subtype of breast cancer. The genes were positively correlated with the proliferation marker Ki67 (p < 0.001). Moreover, moderate positive linear correlations between HK2 and PKM2 (r = 0.476), HK2 and PFKM (r = 0.473), and PKM2 and PFKM (r = 0.501) were also observed (p < 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.

Estrogen Receptor α(ERα) is reported to regulate the expression of many target genes by binding to specific estrogen response elements (EREs) in their promoters. c-myc is known to be over-expressed in most of the human carcinomas due to dysregulated transcription, translation, or protein stability. Estrogen (E) can induce the c-myc expression by binding to an upstream enhancer element in its promoter. This suggests that elevated estradiol (E2), a potent form of estrogen, levels could induce the expression of c-myc in breast cancer (BC). The expression of c-myc and estradiol were induced at Stage III and Stage IV of breast cancer. c-myc and estradiol expression was also associated with the established risk factors of breast cancer, such as BMI. Age at the time of the disease was alsocorrelated with the relative expression of c-myc and estradiol (p < 0.0007 and p < 0.000001). The correlation coefficient (R = 0.462) shows a positive relationship between estradiol bound ER, ER, and c-myc. Docking energy −229 kJ/mol suggests the binding affinity of estradiol bound ER binding to 500 bp upstream of proximal promotor of c-myc at three distinct positions. The data presented in this study proposed that the expression of c-myc and estradiol are directly correlated in breast cancer. The prognostic utility of an induced level of c-myc associated with the normal status of the c-myc gene and estradiol for patients with metastatic carcinoma should be explored further.

The epithelial cell adhesion molecule (EpCAM) is considered an essential proliferation signature in cancer. In the current research study, qPCR induced expression of EpCAM was noted in acute lymphoblastic leukemia (ALL) cases. Costunolide, a sesquiterpene lactone found in crepe ginger and lettuce, is a medicinal herb with anticancer properties. Expression of EpCAM and its downstream target genes (Myc and TERT) wasdownregulated upon treatment with costunolide in Jurkat cells. A significant change in the telomere length of Jurkat cells was not noted at 72 h of costunolide treatment. An in silico study revealed hydrophobic interactions between EpCAM extracellular domain and Myc bHLH with costunolide. Reduced expression of NFκB, a transcription factor of EpCAM, Myc, and TERT in costunolide-treated Jurkat cells, suggested that costunolide inhibits gene expression by targeting NFκB and its downstream targets. Overall, the study proposes that costunolide could be a promising therapeutic biomolecule for leukemia.