GSDMB 在口腔鳞状细胞癌中的表达特征及其对肿瘤免疫微环境和预后的影响

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck region worldwide, with its development influenced by a multitude of factors such as genetic mutations and the immune microenvironment. Despite the availability of current treatment options, issues like drug resistance and recurrence persist. The Gasdermin B (GSDMB) gene encodes the protein Gasdermin B which exhibits complex biological functions in various cancers, notably playing a significant role in cell death and immune responses. However, the role of GSDMB in OSCC remains unclear. Therefore, this study aims to investigate the expression profile of GSDMB in OSCC and its potential biological functions.

This study employs a bioinformatics approach to analyze the expression landscape of GSDMB in OSCC based on multi-omics data. Initially, we analyzed the expression of GSDMB across pan-cancer types and categorized OSCC samples into high and low-expression groups according to the median expression value. Subsequently, differences between these two groups concerning tumor mutation burden (TMB), immune microenvironment, in silico drug sensitivity analysis, and prognosis were explored. Additionally, single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics data (stRNA-seq) were utilized to analyze the expression characteristics of GSDMB across different cell types. To further support the computational prediction, in vitro 5-fluorouracil (5-FU) sensitivity assays were performed in SCC25 cells with or without GSDMB knockdown.

The expression of GSDMB was significantly higher in OSCC tumor tissues compared to normal tissues, with significant differences observed across tumor grades, age groups, and N stages. The TMB was significantly higher in the high-expression group than in the low-expression group, showing a positive correlation between GSDMB expression levels and TMB. Survival analysis revealed that patients in the high-TMB group had significantly lower survival rates compared to those in the low-TMB group, while high GSDMB expression correlated with poorer prognosis. Immune landscape analysis indicated higher infiltration levels of CD8+ T cells and natural killer cells in the high-expression group, along with enhanced immune functions such as antigen presentation, cytotoxic activity, and immune checkpoint activity. In silico drug sensitivity analysis suggested that patients with high GSDMB expression may be more responsive to multiple anticancer agents. Consistently, in SCC25 cells, GSDMB knockdown significantly increased the IC50 of 5-FU, indicating reduced chemosensitivity upon GSDMB depletion. Furthermore, scRNA-seq analysis uncovered differential expression of GSDMB among distinct immune cell populations, suggesting its potential significance in the tumor immune microenvironment.

GSDMB may play a crucial role in the development of OSCC and is closely associated with TMB, the immune microenvironment, and drug response prediction by in silico drug sensitivity analysis. Its expression not only influences the tumor immune response but also has the potential to serve as a biomarker and therapeutic target for OSCC. This study provides novel insights into the functional role of GSDMB in OSCC and its clinical application as a prognostic marker.