Opposite expression of NCOA4 in glioblastoma tissues and cell lines

Recent research has found that ferroptosis is the most prevalent type of programmed cell death in glioma tissues and is associated with malignant progression, poor prognosis, and exacerbated immune suppression in glioblastoma (GBM). In recent years, nuclear receptor coactivator 4 (NCOA4) has been identified as a key protein in ferroptosis, but its expression in GBM tissues remains unclear. We observed an intriguing phenomenon where the expression pattern of NCOA4 was opposite in GBM tissues compared to three GBM cell lines (U87-MG, U251, and LN229), with NCOA4 expression being elevated in brain tissue but decreased in the GBM cells. This observation was further confirmed through bioinformatics analysis and experiments. Based on this finding, we hypothesize that immune cells in GBM tissues may exhibit more pronounced signs of iron depletion compared to tumor cells, which could contribute to the therapeutic resistance of GBM. The increase in NCOA4 observed in tumor tissues does not necessarily reflect increased ferroptosis in tumor cells but might indicate increased ferroptosis in non-tumor cells. This point should be considered when evaluating the efficacy of inducing ferroptosis via NCOA4 in GBM research. This observation could potentially impact the proposed strategy of inducing iron depletion as a treatment for GBM. We recognize the importance of this finding for guiding future GBM research and believe it warrants further investigation. This phenomenon may also be present in other types of tumors.