Prognostic Effect of Glycogen Synthase Kinase 3A (GSK3A) mRNA Expression in Breast Cancer Patients

Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase and regulates glycogen synthase, cellcycle progression and apoptosis. PI3K/PTEN/AKT/GSK3/mTORC1 pathway is often activated in multiple human cancers and activated AKT phosphorylates and inactivates GSK3. GSK3 exists as and isoforms in mammals; however which GSK3 isoform regulates cancer cell proliferation is still unclear. Notably, most studies have focused on GSK3 and very few reports addressed the role of the alpha isoform in cancer. Current study explored the prognostic role of GSK3A in breast cancer patients using Kaplan-Meier plotter (KM plotter). GSK3A mRNA expression was significantly correlated with breast cancer patients survival. Lower GSK3A mRNA expression was significantly correlated to poorer relapse-free survival (RFS) in breast cancer patients (including luminal A and basal type). Luminal A breast cancer patients showed a better RFS with higher GSK3A mRNA expression in systemically untreated and chemotherapy only treated patients. Lower mRNA expression of GSK3A was significantly correlated to poorer RFS in luminal A breast cancer patients with grade 2 tumors and negative lymph node status. The distinct prognostic effect of GSK3A mRNA expression in breast cancer patients thus makes it a potential therapeutic target.