TMEM115: a promising marker for glioma immunotherapy and prognosis

TL;DR

TMEM115 is a protein that is more active in glioma tumors and may help predict patient outcomes and guide immunotherapy.

Contribution

This study identifies TMEM115 as a novel prognostic biomarker and potential immunotherapy target in glioma.

Findings

TMEM115 expression is significantly higher in glioma tissues compared to non-tumor brain tissues.

Knockdown of TMEM115 reduces glioma cell proliferation, migration, and invasion.

TMEM115 correlates with M2 macrophages, PD-L1, and poor patient prognosis in glioma.

Abstract

Glioma is a common malignant primary brain tumor characterized by a highly immunosuppressive tumor microenvironment and unfavorable prognosis. Transmembrane protein 115 (TMEM115) is a protein-coding gene. It may play a role in the retrograde transport of proteins from the Golgi to the endoplasmic reticulum. At the same time, it may also play an indirect role in protein glycosylation at the Golgi. However, the role of TMEM115 in glioma progression is still unclear and, therefore, needs further exploration.

RNA-seq data from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases of glioma patients and multiplex Immunohistochemistry by glioma tissue microarrays were analyzed to determine the expression and localization of TMEM115. Functional assessment of TMEM115 involved cell proliferation, migration, and invasion assays. Pearson’s test was utilized to evaluate the association between TMEM115 protein levels, tumor immune infiltrating cells, and immune checkpoints. In addition, χ2 test and Cox regression analyses were performed to investigate whether TMEM115 protein expression is related to clinical characteristics and patient outcomes.

The results revealed a significant increase in TMEM115 expression in tumors than in non-tumor brain tissues, and knockdown of TMEM115 affects the ability of glioma cell lines to proliferate, migrate, and invade. Additionally, a significant correlation between TMEM115 protein, M2 macrophages (CD68+CD163+), and programmed cell death ligand-1 (PD-L1). Further analysis confirmed a correlation between TMEM115 protein expression in glioma tissues, World Health Organization Grade, and patients’ poorer prognosis.

These findings support TMEM115 as a potential independent prognostic biomarker in glioma and suggest its promise as a target for immunotherapy.

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