A Novel S100 Family-Based Signature Associated with Prognosis and Immune Microenvironment in Glioma

Abstract

Background. Glioma is the most common central nervous system (CNS) cancer with a short survival period and a poor prognosis. The S100 family gene, comprising 25 members, relates to diverse biological processes of human malignancies. Nonetheless, the significance of S100 genes in predicting the prognosis of glioma remains largely unclear. We aimed to build an S100 family-based signature for glioma prognosis. Methods. We downloaded 665 and 313 glioma patients, respectively, from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) database with RNAseq data and clinical information. This study established a prognostic signature based on the S100 family genes through multivariate COX and LASSO regression. The Kaplan–Meier curve was plotted to compare overall survival (OS) among groups, whereas Receiver Operating Characteristic (ROC) analysis was performed to evaluate model accuracy. A representative gene S100B was further verified by in vitro experiments. Results. An S100 family-based signature comprising 5 genes was constructed to predict the glioma that stratified TCGA-derived cases as a low- or high-risk group, whereas the significance of prognosis was verified based on CGGA-derived cases. Kaplan–Meier analysis revealed that the high-risk group was associated with the dismal prognosis. Furthermore, the S100 family-based signature was proved to be closely related to immune microenvironment. In vitro analysis showed S100B gene in the signature promoted glioblastoma (GBM) cell proliferation and migration. Conclusions. We constructed and verified a novel S100 family-based signature associated with tumor immune microenvironment (TIME), which may shed novel light on the glioma diagnosis and treatment.

Construction and validation of an angiogenesis-related gene expression signature associated with clinical outcome and tumor immune microenvironment in glioma

“…Furthermore, we compared the prognostic predictive abilities of 20 different risk signatures of gliomas in TCGA from published articles, including inflammatory response-related gene (IRRG) signature ( Yan et al, 2022 ), DNA damage and repair-related gene (DDRRG) signature ( Li et al, 2022c ), CXCR members signature ( He et al, 2022 ), pyroptosis-related gene signature ( Zhang M. et al, 2021b ; Chao et al, 2022 ; Yang et al, 2022 ; Zhang et al, 2022 ), ECM-related gene (ECMRG) signature ( Li et al, 2022b ), tripartite motif (TRIM) family gene signature ( Xiao et al, 2022 ), antigen presentation machinery (APM) signature ( Chen et al, 2022 ), natural killer cell-related gene (NKRG) signature ( Li C. et al, 2022a ), IL-4-related gene (IL4RG) signature ( Qi et al, 2022 ), hypoxia-related gene (HRG) signature ( Gao et al, 2021 ), S100 family-based signature ( Hu et al, 2021 ), TIME signature ( Zhang C. et al, 2021a ), focal adhesion-related gene (FARG) signature ( Li et al, 2021 ), m6A RNA methylation regulator signature ( Cong et al, 2021 ), HDAC1-related signature ( Fan et al, 2021 ), RNA-binding protein (RBP)-based signature ( Chen et al, 2021a ) and ferroptosis-related gene (FRG) signature ( Chen et al, 2021b ). The results of univariate and multivariate Cox analyses showed that our ARG signature had independent predictive ability ( p < 0.001, Table 1 ).…”

Alarm Signal S100-Related Signature Is Correlated with Tumor Microenvironment and Predicts Prognosis in Glioma

“…S100 protein family participates in multiple pathological and physiological processes, including apoptosis, inflammatory reaction, and cancer progression [ 27 ]. Previous studies have reported the potential prognostic role of the S100A genes and the S100 family genes [ 28 , 29 ]. In current study, we constructed a novel prognostic model based on eight S100 family genes (S100A2-4, S100A8, S100A10-11, S100A16, and S100Z) and demonstrated its effectiveness in predicting the prognosis of gliomas ( Figure 4 and Supplementary Figure 1 ).…”

Highly immune-related genes of breast cancer: potential diagnostic and prognostic biomarkers

“…S100B is a member of the S100 superfamily, which is localized in the cytoplasm and/or nucleus of a wide range of cells and is involved in the regulation of cell proliferation, differentiation, apoptosis, and immune responses (Hua et al 2020). A study found that abnormal expression of S100B in glioblastoma led to changes in the immune microenvironment; this promotes the proliferation and migration of tumor cells (Hu et al 2021). In this context, high S100B expression has been found to predict good OS in estrogen negative-breast cancer patients and good distant metastasis-free survival in all breast cancer patients (Yen et al 2018).…”