Differential Site-Based Expression of Pentose Phosphate Pathway-Related Proteins among Breast Cancer Metastases

Purpose. We aimed to investigate the expression of pentose phosphate pathway- (PPP-) related proteins in metastatic breast cancer and its relationship with clinicopathologic factors. Methods. Tissue samples from 126 metastatic breast cancers were included in a tissue microarray. Expression of PPP-related proteins [glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconolactonase (6PGL), 6-phosphogluconate dehydrogenase (6PGDH), and nuclear factor erythroid 2-related factor (NRF2)] was determined by immunohistochemistry. Results. G6PDH (p=0.011) and cytoplasmic NRF2 (p=0.001) showed the highest expression in brain metastases. Human epidermal growth factor receptor (HER-2) positivity was associated with G6PDH (p<0.001) and cytoplasmic NRF2 (p=0.015) positivity. A high Ki-67 labeling index (LI) was correlated with nuclear NRF2 positivity (p=0.037), and HER-2-positive luminal B type was associated with G6PDH positivity (p=0.001). On multivariate Cox analysis, independent risk factors of short overall survival were 6PGL positivity in bone metastasis (HR 4.180, 95% CI 1.160-15.06, p=0.029) and low Ki-67 LI in lung metastasis (HR 11.853, 95% CI 1.841-76.30, p=0.009). Conclusion. Differential expression of PPP-related proteins correlated with different prognoses and metastatic sites, with the highest expression in brain metastases, and could be a potential therapeutic target.