Pan-cancer analysis of Sp1 with a focus on immunological roles in gastric cancer

Abstract Background Sp1, a transcription factor, plays a pivotal role in tumorigenesis across diverse cancers. However, its comprehensive pan-cancer analyses and immunological roles in gastric cancer (GC) remain inadequately elucidated. Methods Through a comprehensive analysis utilizing bioinformatics tools and datasets from TCGA, GEO, and THPA, we examined the multifaceted role of Sp1. Expression profiles were assessed across cell lines, tissues, and tumors, alongside exploration of genetic alterations, DNA methylation, and protein phosphorylation. Its associations with immune infiltration, tumor mutational burden, and immune checkpoint signaling were investigated. Additionally, single-cell transcriptome data showed its expression in different immune cells in GC. Validation of correlations between Sp1 and immune microenvironment in GC was performed using immunohistochemistry and multiple immunofluorescence in an immunotherapy-treated patient cohort. The prognostic value of Sp1 in GC receiving immunotherapy was evaluated with Cox regression model. Results Elevated Sp1 levels were observed in various cancers compared to normal tissues, with notable prominence in gastric cancer. High Sp1 expression correlated with advanced stage, poor prognosis, elevated tumor mutational burden (TMB), and microsatellite instability (MSI) status, particularly in GC. Sp1 levels also correlated with CD8 + T cell and M1 phenotype of tumor-associated macrophages infiltration. Furthermore, GC patients with higher Sp1 levels exhibited improved response to immunotherapy. Moreover, Sp1 emerged as a prognostic and predictive biomarker for GC patients undergoing immunotherapy. Conclusions Our pan-cancer analysis sheds light on Sp1's multifaceted role in tumorigenesis and underscores its potential as a prognostic and predictive biomarker for GC patients undergoing immunotherapy.