Forkhead-box-P family include FOXP1/2/3/4 and its clinical significance still remains unclear in breast cancer (BRCA). We analysed the expressions of FOXPs in BRCA patients to determine diagnostic and prognostic values. Our results indicated that the transcriptional levels of FOXP3/4 were up-regulated in BRCA patients, but FOXP2 were down-regulated. No statistically significant correlation were found between the expression levels of FOXPs in Pathologic stage. FOXP2/3 had a significantly high AUC value in the detection of breast cancer, with 96.8% or 95.7% in accuracy respectively. Our study also suggested that BRCA patients with high transcription levels of FOXP1/2/4 were significantly associated with longer Overall Survival (OS). In contrast, BRCA patients with high transcription level of FOXP3 was not statistically related with OS. Our work revealed that FOXPs were closely related to the alteration of extensive immune checkpoints in breast invasive carcinoma. Additionally, FOXP3 has a significant positive correlation with PDCD1, CD274, CTLA4 and TMB in breast cancer, and FOXP3 expression showed a statistically significant correlation with infiltration of immune cells. Finally, we found that FOXP3 expression predicted the breast cancer cells response to anticancer drugs. Altogether, our work strongly suggested that FOXPs could serve as a biomarker for tumor detection, therapeutic design and prognosis.

Glucose-6-phosphate isomerase (GPI) plays an important part in gluconeogenesis and glycolysis through the interconversion of d-glucose-6-phosphate and d-fructose-6-phosphate, and its clinical significance still remains unclear in breast cancer (BRCA). We analyzed the expressions of GPI in BRCA patients to determine prognostic values. Our results showed that the expression levels of GPI were upregulated in BRCA patients, and a high GPI expression is correlated with poor overall survival (OS) in BRCA. At the same time, a high GPI expression is correlated with poor clinicopathological characteristics, such as stage III, over 60 years old, N3, HER2 negative, and estrogen receptor (ER) positive. Further analysis of the influence of GPI on the prognosis of BRCA suggested that 50 genes and 10 proteins were positively correlated with GPI, and these genes and proteins were mainly involved in cell cycle signaling pathways. In addition, in this study, we observed that GPI was closely related to N6-methyladenosine (m6A) RNA methylation modification and immune cell infiltration and ferroptosis-related gene expression in BRCA, and there was a difference in m6A RNA methylation alterations, immune cell infiltration, and ferroptosis-related gene expression between the high GPI expression group and the low GPI expression group. Finally, we found that GPI in BRCA had 2.6% gene alterations, and BRCA patients with gene alteration of GPI had a poor prognosis in disease-free survival (DFS). Altogether, our work strongly suggested that GPI may serve as a new prognostic biomarker for BRCA patients.