Clinical Significance Of FERMT3 Expression And Its Correlation With Tumor Immune Microenvironment In Gliomas

Objective:To investigate the expression of FERMT3 and Kindlin-3(integrin-activated protein)in gliomas and its relationship with tumor prognosis,gene mutation,functional pathways and immune microenvironment,and to provide a new therapeutic target for the precision treatment of glioma.Methods:The expression of FERMT3 and its encoding protein Kindlin-3 in gliomas was analyzed by bioinformatics.The relationship between FERMT3 and tumor prognosis,gene mutations,functional pathways and immune microenvironment was further analyzed by multiple datasets to predict its relationship with immunotherapeutic response and potentially relevant small molecule compounds.The expression of Kindlin-3 in clinical glioma samples was verified by immunohistochemistry,and the expression of Kindlin-3 in Glioma-associated microglia and macrophages(GAMs)was verified by multiple fluorescence immunohistochemical staining.Results:FERMT3 is an independent predictor of glioma prognosis and is highly expressed in glioblastoma tissues.Functional enrichment analysis showed that FERMT3 was involved in several immune-related pathways,such as immune response and cytokine production.In addition,FERMT3 expression was positively correlated with infiltration of several immune cells,immune scores,and expression of genes associated with immune checkpoints.Further analysis showed that high FERMT3 expression was associated with a better response to anti-PD1 therapy.Analysis of single-cell RNA-seq data showed that FERMT3 was abundantly expressed in microglia and tissue-resident macrophages.Multiplex fluorescence immunohistochemical staining showed that Kindlin-3 was co-expressed with the pan-myeloid marker IBA1 and the microglial cell marker TMEM119.Conclusions:FERMT3 is closely related to the clinicopathological features of glioma and can be used as an independent prognostic indicator.FERMT3 was involved in immune-related pathways such as immune response and cytokine production,and its encoded protein Kindlin-3 may play a crucial role in glioma progression and targets glioma-associated microglia and macrophages(GAMs),which is expected to be a new target for immunotherapy of glioma.