ArticleFrontiers in oncology2021
The Correlation Between SPP1 and Immune Escape of EGFR Mutant Lung Adenocarcinoma Was Explored by Bioinformatics Analysis.
Article in Frontiers in oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature.Frontiers in immunology · 2023Pooled it
- Multi-omics profiling identifies ESM1 as a key mediator of immunoevasion through the SPP1 pathway in bladder cancer.Scientific reports · 2025Article
- The Multifaceted Role of Osteopontin in Modulating the Tumor Microenvironment.Cancer research · 2025Review
- Combined anti-SPP-1 and anti-CTLA-4 immunotherapy enhances anti-tumor efficacy in hepatocellular carcinoma via IL-6/STAT3 pathway modulation.Cytotechnology · 2025Article
- Distinct immune cell infiltration patterns in pancreatic ductal adenocarcinoma (PDAC) exhibit divergent immune cell selection and immunosuppressive mechanisms.Nature communications · 2025Article
- Tp53 determines the spatial dynamics of M1/M2 tumor-associated macrophages and M1-driven tumoricidal effects.Cell death & disease · 2025Article
- Study on the Mechanism of Competing Endogenous Network of 'Current computer-aided drug design · 2025Article
- Article
- Upregulation of CKS2 in immunosuppressive cells is associated with metastasis and poor prognosis in prostate cancer: a single-cell RNA-sequencing analysis.Translational cancer research · 2024Article
- Osteopontin/SPP1: a potential mediator between immune cells and vascular calcification.Frontiers in immunology · 2024Review
- Article
- Biomarkers of lung cancer for screening and in never-smokers-a narrative review.Translational lung cancer research · 2023Review
- Activin A-Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Single-cell RNA-seq analyses inform necroptosis-associated myeloid lineages influence the immune landscape of pancreas cancer.Frontiers in immunology · 2023Article
- High-resolution single-cell atlas reveals diversity and plasticity of tissue-resident neutrophils in non-small cell lung cancer.Cancer cell · 2022Article
- Emerging strategies to overcome resistance to third-generation EGFR inhibitors.Journal of hematology & oncology · 2022Review
- Identification of Immune-Related Prognostic mRNA and lncRNA in Patients with Hepatocellular Carcinoma.Journal of oncology · 2022Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint inhibitors have achieved breakthrough efficacy in treating lung adenocarcinoma (LUAD) with wild-type epidermal growth factor receptor (EGFR), leading to the revision of the treatment guidelines. However, most patients with EGFR mutation are resistant to immunotherapy. It is particularly important to study the differences in tumor microenvironment (TME) between patients with and without EGFR mutation. However, relevant research has not been reported. Our previous study showed that secreted phosphoprotein 1 (SPP1) promotes macrophage M2 polarization and PD-L1 expression in LUAD, which may influence response to immunotherapy. Here, we assessed the role of SPP1 in different populations and its effects on the TME.
methodsWe compared the expression of SPP1 in LUAD tumor and normal tissues, and in samples with wild-type and mutant EGFR. We also evaluated the influence of SPP1 on survival. The LUAD data sets were downloaded from TCGA and CPTAC databases. Clinicopathologic characteristics associated with overall survival in TCGA were assessed using Cox regression analysis. GSEA revealed that several fundamental signaling pathways were enriched in the high SPP1 expression group. We applied CIBERSORT and xCell to calculate the proportion and abundance of tumor-infiltrating immune cells (TICs) in LUAD, and compared the differences in patients with high or low SPP1 expression and wild-type or mutant EGFR. In addition, we explored the correlation between SPP1 and CD276 for different groups.
resultsSPP1 expression was higher in LUAD tumor tissues and in people with EGFR mutation. High SPP1 expression was associated with poor prognosis. Univariate and multivariate cox analysis revealed that up-regulated SPP1 expression was independent indicator of poor prognosis. GSEA showed that the SPP1 high expression group was mainly enriched in immunosuppressed pathways. In the SPP1 high expression group, the infiltration of CD8+ T cells was lower and M2-type macrophages was higher. These results were also observed in patients with EGFR mutation. Furthermore, we found that the SPP1 expression was positively correlated with CD276, especially in patients with EGFR mutation.
conclusionSPP1 levels might be a useful marker of immunosuppression in patients with EGFR mutation, and could offer insight for therapeutics.
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