SPP1 in Immunosuppressive Signaling in Lung Adenocarcinoma: Bulk and Single-Cell Transcriptomic Analysis
Lijun Jiao1, Xiantao Xu1, Yantong Liu2
1Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Yangzhou University, Yangzhou, China.
Cell Biochemistry and Biophysics
|May 28, 2026
Summary
Secreted phosphoprotein 1 (SPP1) is linked to poor prognosis in lung adenocarcinoma (LUAD). High SPP1 expression correlates with immune suppression and worse survival, suggesting it as a prognostic biomarker.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Secreted phosphoprotein 1 (SPP1) is implicated in various cancers, correlating with immune infiltration and poor prognosis.
- Its role in lung adenocarcinoma (LUAD) tumor microenvironment (TME) intercellular communication is not well understood.
Purpose of the Study:
- Investigate the prognostic value of SPP1 in LUAD.
- Analyze SPP1's association with intercellular communication patterns within the LUAD TME.
Main Methods:
- Integrated bulk and single-cell RNA-seq data (GSE7670, GSE43458, TCGA-LUAD, GSE123902).
- Utilized protein-protein interaction networks, CytoHubba, Seurat, SingleR, and CellChat for analysis.
- Assessed immune infiltration, immune checkpoints, and survival outcomes.
Main Results:
- SPP1 was overexpressed in LUAD, primarily secreted by macrophages and monocytes.
- SPP1 signaling via CD44 and integrins was a prominent pattern in the LUAD TME.
- High SPP1 correlated with increased regulatory T cells, MDSCs, immunosuppressive checkpoints (CD276, PDCD1LG2), EMT, PI3K-AKT activation, and worse survival.
Conclusions:
- SPP1 may serve as a prognostic biomarker and immune communication molecule in LUAD.
- Findings suggest SPP1 is associated with immunosuppressive remodeling in the LUAD microenvironment.
- Further validation is needed, but SPP1 may inform LUAD immunotherapy strategies.
