SMPD2 affects the prognosis of cancer patients by mediating lipid metabolism and the immune microenvironment

The gene Sphingomyelin phosphodiesterase 2 (SMPD2), a member of the SMPD family, plays crucial roles in cell cycle progression and cell proliferation. However, the pathogenic implications of SMPD2 across various cancers remain poorly understood. Its potential involvement in lipid metabolism and immune-related processes within the tumor microenvironment has not been systematically characterized. To address these gaps, we conducted a comprehensive pan-cancer analysis of SMPD2. Using a range of computational tools, we investigated its role in tumor immune infiltration, immune evasion, tumor progression, therapy response, and prognosis across various cancer types. Our findings suggest that SMPD2 is widely expressed across cancers in The Cancer Genome Atlas (TCGA) and its expression levels are associated with tumor stages and clinical outcomes. Additionally, SMPD2 was found to be involved in tumor immune evasion across different cancer types. The methylation status of SMPD2 was inversely correlated with its mRNA expression levels, which were associated with dysfunctional T cell phenotypes and worse prognoses in diverse cancer cohorts. Furthermore, SMPD2 expression was linked to heterogeneous therapeutic outcomes across multiple cancer types, including variable responses to immune checkpoint blockade. Interestingly, SMPD2 demonstrated superior predictive capacity for treatment response and overall survival in immune checkpoint blockade sub-cohorts compared to three of the seven established biomarkers. While functional experiments are warranted, our results provide a data-driven, pan-cancer landscape of SMPD2 expression and its potential relevance to immune modulation and clinical outcomes Overall, SMPD2 may serve as a candidate biomarker for cancer prognosis and therapeutic response, and a potential target for future mechanistic studies.