A comprehensive analysis of the prognostic value and immune microenvironment of lysosome-dependent cell death in glioma - Including glioblastoma and low-grade glioma

Q: What is the main goal of this study on lysosome-dependent cell death in glioma?

To determine how LCD-associated genes relate to glioma prognosis and the immune microenvironment, including glioblastoma and low-grade glioma.

Q: How was the LCDGs risk signature constructed and evaluated?

Core LCDGs were identified using Extreme Gradient Boosting, Support Vector Machine, Random Forest, and Generalized Linear Models, and then their associations with clinical features and immune characteristics were analyzed.

Q: Why is LAPTM4A highlighted as a hub gene?

Differential expression and validation analyses showed LAPTM4A is upregulated in glioma, glioblastoma, and low-grade glioma, and its expression correlates with prognosis and multiple clinical variables; pan-cancer results and mechanistic analyses connect it to immune infiltration and drug sensitivities.

Sep 21, 2026

Uploaded by Patrick

Lysosome-dependent cell death (LCD) influences cancer apoptosis and resistance, yet how LCD-associated genes relate to glioma immune biology remains unclear. This study built an LCDGs risk signature for glioma using four machine-learning algorithms to identify core LCDGs and assess links with clinical traits and immune microenvironments across glioblastoma and low-grade glioma. Hub gene LAPTM4A was validated by qRT-qPCR and immunofluorescence, showing diagnostic and prognostic associations. Mechanistic analyses further linked the signature and LAPTM4A to immune cell infiltration and drug sensitivities, supporting individualized glioma treatment potential.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Introduction

Background on glioma and immune resistance

Study rationale and biomarker need

® Observational Study A comprehensive analysis of the prognostic value and immune microenvironment of lysosomedependent cell death in glioma Including glioblastoma and low-grade glioma Wei Li, MDa ,* , Jun Wang, MDa , Chao Tang, MDa | Abstract
Lysosome-dependent cell death (LCD) plays a significant role in overcoming cancer apoptosis and drug resistance. However, the relationship between LCD-associated genes (LCDGs) and glioma, including glioblastoma (GBM) and low-grade glioma (LGG), remains unclear. In this study, an LCDGs risk signature was constructed for glioma patients by utilizing 4 algorithms (Extreme Gradient Boosting, Support Vector Machine, Random Forest, and Generalized Linear Models) to identify core LCDGs. Their correlation with clinical features and the immune microenvironment was also determined in glioma, GBM, and LGG. Additionally, the role of hub LCDGs in various cancers was elucidated via pan-cancer analyses. Validation of the core gene in glioma was performed using qRT-qPCR and immunofluorescence staining analysis. The results showed that the LCDGs risk signature was strongly associated with the prognosis, cancer grades, histological types, and primary therapy outcomes of glioma patients. Furthermore, it was closely linked to the overall survival of LGG patients. Mechanistic analyses revealed a significant association between the risk signature and the immune microenvironment in glioma. Based on differential expression analysis, receiver operating characteristic analysis, and interacted model algorithms, LAPTM4A was identified as a hub LCDG in glioma. It exhibited significant upregulation in glioma, GBM, and LGG samples. Moreover, LAPTM4A expression correlated with the prognosis of glioma and LGG patients, as well as age, grades, histological types, and primary therapy outcomes in glioma. Pan-cancer analysis confirmed that LAPTM4A expression was modulated in the majority of cancers and was associated with the prognosis of various cancers. Mechanistic analyses suggested a strong relationship between LAPTM4A and immune cell infiltration, as well as several drug sensitivities. In conclusion, our findings suggest that LAPTM4A may serve as a potential oncogene associated with LCD in pan-cancer, particularly in glioma, GBM, and LGG. These findings provide important insights for individualized treatment of glioma. | | --- | | Abbreviations: FC = fold change, GBM = glioblastoma, GTEx = Genotype-Tissue Expression, LASSO = least absolute shrinkage and selection operator, LCD = lysosome-dependent cell death, LCDGs = LCD-associated genes, LGG = low-grade glioma, OS = overall survival, ROC = receiver operating characteristic, TCGA = The Cancer Genome Atlas. | | Keywords: glioma, immune microenvironment, LAPTM4A, lysosome-dependent cell death, pan-cancer | 1. Introduction Glioma, the most prevalent primary malignant brain tumor, accounts for 81% of malignancies in the central nervous system.[1] It is a heterogeneous neoplasm that ranges from surgically curable low-grade glioma (LGG) to glioblastoma (GBM) .[2] GBM constitutes over 50% of all gliomas and is considered the most invasive and virtually incurable type, with a 5-year survival probability of <3% .[3] Despite significant progress in surgical operation treatment, chemotherapy, and radiotherapy, the overall survival (OS) of patients with glioma remains very unfavorable. Immunotherapy offers promise as a treatment for malignant cancers.[4] However, due to the presence of an immunosuppressive tumor microenvironment, glioma patients are usually resistant to immune checkpoint inhibitors, ultimately leading to a poor prognosis.[5,6] Therefore, urgently needed are the identification and screening of novel treatment approaches and immunotherapy molecular biomarkers, as well as the construction of prognostic signatures capable of accurately predicting a patient’s condition. The authors have no funding and conflicts of interest to disclose. The data

FAQs

What is the main goal of this study on lysosome-dependent cell death in glioma?

To determine how LCD-associated genes relate to glioma prognosis and the immune microenvironment, including glioblastoma and low-grade glioma.

How was the LCDGs risk signature constructed and evaluated?

Core LCDGs were identified using Extreme Gradient Boosting, Support Vector Machine, Random Forest, and Generalized Linear Models, and then their associations with clinical features and immune characteristics were analyzed.

Why is LAPTM4A highlighted as a hub gene?

Differential expression and validation analyses showed LAPTM4A is upregulated in glioma, glioblastoma, and low-grade glioma, and its expression correlates with prognosis and multiple clinical variables; pan-cancer results and mechanistic analyses connect it to immune infiltration and drug sensitivities.

Sep 21, 2026

Uploaded by Patrick