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S100A8 is a prognostic signature and associated with immune response in diffuse large B-cell lymphoma
Qi Lin1,2, Jianlin Su2, Yuanyuan Fang2
1Department of Pharmacy, The Affiliated Hospital of Putian University, Putian, Fujian, China.
Insights
Elevated S100A8 expression correlates with poor prognosis in Diffuse Large B-cell Lymphoma (DLBCL). Inhibiting S100A8 promotes apoptosis and suppresses tumor growth, suggesting its potential as an immunotherapeutic target for DLBCL.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- S100A8, a calcium-binding protein, is implicated in immune responses and tumor development.
- Diffuse Large B-cell Lymphoma (DLBCL) presents a significant challenge, with 40% of patients remaining incurable.
- The specific role of S100A8 in DLBCL's immune response is not well understood.
Purpose of the Study:
- To investigate the role and prognostic significance of S100A8 in Diffuse Large B-cell Lymphoma (DLBCL).
- To explore the functional impact of S100A8 on DLBCL progression and the tumor microenvironment.
- To evaluate S100A8 as a potential therapeutic target for DLBCL.
Main Methods:
- Differential gene expression analysis using GEO and TCGA databases.
- Prognostic analysis via Kaplan-Meier curves and functional enrichment (GO, KEGG, GSEA, PPI).
- In vitro experiments involving S100A8 inhibition, single-cell RNA sequencing, and immune cell infiltration analysis.
Main Results:
- S100A8 was significantly overexpressed in DLBCL and associated with poor prognosis.
- Functional enrichment highlighted the IL-17 signaling pathway; in vitro studies showed S100A8 inhibition promotes apoptosis and suppresses tumor growth.
- S100A8 expression correlated with tumor microenvironment features and immune cell infiltration, with potential drug sensitivities identified.
Conclusions:
- High S100A8 expression is linked to poor prognosis and immune infiltration in DLBCL.
- Inhibiting S100A8 demonstrates therapeutic potential by promoting apoptosis and reducing tumor growth.
- S100A8 emerges as a promising immunotherapeutic target for DLBCL patients.
Background:
S100A8, a calcium-binding protein belonging to the S100 family, is involved in immune responses and multiple tumor pathogens. Diffuse large B-cell lymphoma (DLBCL) is one of the most common types of B-cell lymphoma and remains incurable in 40% of patients. However, the role of S100A8 and its regulation of the immune response in DLBCL remain unclear.
Methods:
The differential expression of S100A8 was identified via the GEO and TCGA databases. The prognostic role of S100A8 in DLBCL was calculated using the Kaplan-Meier curve. The function enrichment of differentially expressed genes (DEGs) was explored through GO, KEGG, GSEA, and PPI analysis. In our cohort, the expression of S100A8 was verified. Meanwhile, the biological function of S100A8 was applied after the inhibition of S100A8 in an in vitro experiment. The association between S100A8 and immune cell infiltration and treatment response in DLBCL was analyzed.
Results:
S100A8 was significantly overexpressed and related to a poor prognosis in DLBCL patients. Function enrichment analysis revealed that DEGs were mainly enriched in the IL-17 signaling pathway. Our cohort also verified this point. In vitro experiments suggested that inhibition of S100A8 should promote cell apoptosis and suppress tumor growth. Single-cell RNA sequence analysis indicated that S100A8 might be associated with features of the tumor microenvironment (TME), and immune infiltration analyses discovered that S100A8 expression was involved in TME. In terms of drug screening, we predicted that many drugs were associated with preferable sensitivity.
Conclusion:
Elevated S100A8 expression is associated with a poor prognosis and immune infiltration in DLBCL. Inhibition of S100A8 could promote cell apoptosis and suppress tumor growth. Meanwhile, S100A8 has the potential to be a promising immunotherapeutic target for patients with DLBCL.
