AUTHOR=Wu Hongrong , He Haoyang , Huang Jiexiong , Wang Chuan , Dong Yuejiao , Lin Ruilin , Cheng Zhuofeng , Qiu Qiancheng , Hong LiangLi 

TITLE=Identification and validation of transferrin receptor protein 1 for predicting prognosis and immune infiltration in lower grade glioma

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 15 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2022.972308

DOI=10.3389/fnmol.2022.972308

ISSN=1662-5099

ABSTRACT=Abstract
TFRC, an Ananda molecule associated with ferroptosis, has been identified as affecting a wide spectrum of pathological processes in various cancers, but the prognostic value and correlates with the tumor microenvironment of TFRC in lower-grade glioma (LGG) are still unclear.
Methods
Clinical pathological information and gene expression data of LGG patients come from The Cancer Genome Atlas (TCGA), CGGA, GTEx, Oncomine, UCSC Xena, and GEO databases. We then used various bioinformatics methods and mathematical models to analyze those data， aiming to investigate the clinical significance of TFRC in LGG and illustrate its association with tumor immunity. In addition, the molecular function, and mechanisms of TFRC were revealed by GO, KEGG, and GSEA. Immunohistochemical experiments analysis has been performed.
Results
TFRC expression was highly expressed in many tumors and showed a poor prognosis. Including gliomas. and it was significantly associated with several poor clinical prognostic variables, tumor immune microenvironment, tumor mutational burden (TMB), m6a modification, and ferroptosis in LGG. TFRC as a key factor was further used to build a prediction nomogram. The C-index, calibration curve, and decision curve analysis showed the nomogram was clinically useful and calibration was accurate. At the same time, we also demonstrated that promoter hypomethylation of DNA upstream of TFRC could lead to high TFRC expression and poor overall survival. There is a significant correlation between TFRC and CD8+T cell, macrophage cell infiltration, and several immune checkpoints, such as PD-L1(cd274), CTLA4, and PD1, suggesting a novel direction for future clinical application. Functional and molecular mechanism analysis showed an association of TFRC expression with immune-related pathways through GSEA, GO, and KEGG analysis. Finally, immunohistochemical experiments confirmed the expression of TFRC and PD-L1 in glioma.
Conclusions
TFRC may be a potential prognostic biomarker and an immunotherapeutic target for glioma.