Molecular and Clinical Characterization of LIGHT/TNFSF14 Expression at Transcriptional Level via 998 Samples With Brain Glioma.

Ying Yang,Shihai Xu,Wen Lv,Aijun Shan,Fei Shi,Jin Wang

doi:10.3389/fmolb.2021.567327

Ying Yang, Shihai Xu + Show 4 more

Open Access

https://doi.org/10.3389/fmolb.2021.567327

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Abstract

LIGHT, also termed TNFSF14, has been reported to play a vital role in different tumors. However, its role in glioma remains unknown. This study is aimed at unveiling the characterization of the transcriptional expression profiling of LIGHT in glioma. We selected 301 glioma patients with mRNA microarray data from the CGGA dataset and 697 glioma patients with RNAseq data from the TCGA dataset. Transcriptome data and clinical data of 998 samples were analyzed. Statistical analyses and figure generation were performed with R language. LIGHT expression showed a positive correlation with WHO grade of glioma. LIGHT was significantly increased in mesenchymal molecular subtype. Gene Ontology analysis demonstrated that LIGHT was profoundly involved in immune response. Moreover, LIGHT was found to be synergistic with various immune checkpoint members, especially HVEM, PD1/PD-L1 pathway, TIM3, and B7-H3. To get further understanding of LIGHT-related immune response, we put LIGHT together with seven immune signatures into GSVA and found that LIGHT was particularly correlated with HCK, LCK, and MHC-II in both datasets, suggesting a robust correlation between LIGHT and activities of macrophages, T-cells, and antigen-presenting cells (APCs). Finally, higher LIGHT indicated significantly shorter survival for glioma patients. Cox regression models revealed that LIGHT expression was an independent variable for predicting survival. In conclusion, LIGHT was upregulated in more malignant gliomas including glioblastoma, IDH wildtype, and mesenchymal subtype. LIGHT was mainly involved in the immune function of macrophages, T cells, and APCs and served as an independent prognosticator in glioma.

Highlights

In the brain, glioma accounts for the most common and malignant primary tumor in adult patients (Meng et al, 2020)
The results of both Chinese Glioma Genome Atlas (CGGA) and TCGA cohorts consistently showed a statistically significant positive correlation between LIGHT expression and WHO grade of glioma (Figures 1A, E), suggesting that a higher LIGHT level was paralleled with higher malignancy in glioma
When patients were further subclassified with respect to IDH mutation status, IDH wildtype glioma was found to be more associated with an increased pattern of LIGHT expression in both datasets, though a statistical significance was not detected in some subgroups (Figures 1B, F)

Summary

Introduction

Glioma accounts for the most common and malignant primary tumor in adult patients (Meng et al, 2020). Role of LIGHT in Glioma et al, 2015; Qiao et al, 2017), prostate tumor (Yan et al, 2015), breast cancer (Gantsev et al, 2013), and melanoma (Hehlgans and Männel, 2001). In melanoma (Hehlgans and Männel, 2001), colorectal cancer (Maker et al, 2015; Qiao et al, 2017), and prostate cancer (Yan et al, 2015), a higher level of LIGHT expression was associated with a better prognosis. While for patients with NSCLC (Brunetti et al, 2020), multiple myeloma (Brunetti et al, 2014; Brunetti et al, 2018), and breast cancer (Gantsev et al, 2013), an increased pattern of LIGHT expression predicted a much worse survival

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