Expression of Pentose Phosphate Pathway-Related Proteins in Breast Cancer

PURPOSE: The purpose of this study was to assess the expression of pentose phosphate pathway- (PPP-) related proteins and their significance in clinicopathologic factors of breast cancer. METHODS: Immunohistochemical staining for PPP-related proteins (glucose-6-phosphate dehydrogenase [G6PDH], 6-phosphogluconolactonase [6PGL], 6-phosphogluconate dehydrogenase [6PGDH], and nuclear factor-erythroid 2-related factor 2 [NRF2]) was performed using tissue microarray (TMA) of 348 breast cancers. mRNA levels of these markers in publicly available data from the Cancer Genome Atlas project and Kaplan-Meier plotters were analyzed. RESULTS: Expression of G6PDH and 6PGL was higher in HER-2 type (p < 0.001 and p = 0.009, resp.) and lower in luminal A type. 6PGDH expression was detected only in TNBC subtype (p < 0.001). G6PDH positivity was associated with ER negativity (p = 0.001), PR negativity (p = 0.001), and HER-2 positivity (p < 0.001), whereas 6PGL positivity was associated with higher T stage (p = 0.004). The 562 expression profile from the TCGA database revealed increased expression of G6PDH and 6PG in the tumor compared with normal adjacent breast tissue. The expression of G6PDH was highest in HER-2 type. HER-2 and basal-like subtypes showed higher expression of 6PGDH than luminal types. CONCLUSION: PPP-related proteins are differentially expressed in breast cancer according to molecular subtype, and higher expression of G6PDH and 6PGL was noted in HER-2 subtype.