GLS and GOT2 as prognostic biomarkers associated with dendritic cell and immunotherapy response in breast cancer.

ABSTRACT

Breast cancer is the females' most common cancer. Targeting the immune microenvironment is a new and promising treatment method for breast cancer. Nevertheless, only a small section of patients can profit by immunotherapy, and improving the ability to accurately predict the potential for immunotherapy response is still awaiting further exploration. In this study, we found that the key factors of glutamine metabolism, glutaminase 1 (GLS) and mitochondrial aspartate transaminase (GOT2), showed opposite expression patterns in breast cancer samples. Based on the expression level of GLS and GOT2, we divided the breast cancer samples into two clusters Cluster 2 showed GLS expressed higher and GOT2 expressed lower, whereas Cluster 1 showed GOT2 expressed higher and GLS expressed lower. GSEA showed that the clusters were related to pathways of immunity. Further analysis showed that Cluster 2 was positively associated with immunity infiltration. Through WGCNA, we identified a module strongly correlated with glutamine metabolism and immunity and identified 11 dendritic cell-associated genes involved in dendritic cell development, maturation, activation and other functions. In addition, Cluster 2 also showed higher immune checkpoint gene expression, which suggest the Cluster 2 had even better response to immunotherapy. The validation dataset could also be clustered into two groups. Cluster 2 (GLS expressed higher and GOT2 expressed lower) of the validation dataset was also positively associated with dendritic cells and a better immunotherapy response. Thus, these data indicate that GLS and GOT2 are prognostic biomarkers which closely related to dendritic cells and better reacted to immunotherapy in breast cancer.