Prognostic Value of IGFBP6 in Breast Cancer: Focus on Glucometabolism

Insulin-like growth factor binding protein 6, identified as a member of the broader insulin-like growth factor binding protein family, exhibits a particular inhibitory action against insulin-like growth factor II. This specific inhibition suggests a potential role for IGFBP6 in controlling the development of malignant tumors that exhibit an overabundance of IGF-II. Type 2 diabetes, a fundamental condition characterized by disruptions in glucose metabolism, is known to be influenced by signaling pathways involving insulin-like growth factors. To investigate the potential mechanisms through which IGFBP6 might function in the metabolic processes and prognostic outcomes of breast cancer, a bioinformatics analysis was conducted utilizing data from The Cancer Genome Atlas database. Furthermore, clinical samples were obtained from breast cancer patients with and without a concurrent diagnosis of type 2 diabetes. These samples were used to compare and validate the prognostic significance of IGFBP6 expression levels.

The findings of this investigation revealed a positive correlation between the levels of all six IGF binding proteins, specifically IGFBP1 through IGFBP6, and the overall survival rates observed in patients diagnosed with breast cancer. Notably, IGFBP6 demonstrated higher levels of expression in breast cancer that was positive for the estrogen receptor. Moreover, patients whose breast cancer was positive for both the estrogen receptor and the progesterone receptor exhibited greater expression levels of IGFBP6 when compared to patients whose tumors were negative for either of these hormone receptors. The study’s results also indicated that IGFBP6 could serve as an independent factor in predicting the prognosis of breast cancer. It was observed that the expression of IGFBP6 was generally lower in breast cancer tissue samples. Furthermore, breast cancer tissue obtained from patients who also had type 2 diabetes showed even lower levels of IGFBP6 expression compared to breast cancer tissue from patients without diabetes.

Further analysis suggested that IGFBP6 is significantly involved in the PI3K-Akt and TGF-beta signaling pathways, as well as in the regulation of the tumor microenvironment. Regarding metabolic processes, the expression of IGFBP6 displayed a negative correlation with the expression of a majority of genes associated with glucose metabolism. Additionally, the expression levels of IGFBP6 were found to be mainly correlated with the presence of mutations in the TP53, PIK3CA, CDH1, and MAP3K1 genes. Beyond its prognostic implications and involvement in metabolic pathways, the study also indicated that increased expression of IGFBP6 in breast cancer cells was associated with enhanced sensitivity to several chemotherapy drugs, including docetaxel, paclitaxel, and gemcitabine.

In conclusion, the collective findings of this research suggest that high expression levels of IGFBP6 are linked to a more favorable prognosis in patients with breast cancer, particularly in those who do not also have type 2 diabetes. Tenalisib IGFBP6 appears to play a role not only in maintaining the characteristics of the tumor microenvironment within breast cancer but also in inhibiting the energy production of cancer cells through its influence on pathways related to glucose metabolism. These observations may offer a novel perspective on the potential utility of IGFBP6 as a marker for predicting the course of breast cancer.