ArticleJournal of the National Cancer Institute2022
SRGN-Triggered Aggressive and Immunosuppressive Phenotype in a Subset of TTF-1-Negative Lung Adenocarcinomas.
Article in Journal of the National Cancer Institute, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 78 citations in OpenAlex.
- Spatial and single-cell transcriptomic profiling reveals interplay between SRGN-associated epithelial programs and C1QC+ macrophages in early LUAD progression.Journal of translational medicine · 2026Article
- Serglycin Across the Disease Spectrum: A Multifunctional Proteoglycan in Inflammation and Cancer.Current issues in molecular biology · 2026Article
- ALKBH5 facilitates Srgn stability via m6A demethylation to disrupt blood-testis barrier integrity in the high-fat diet mice.Cellular and molecular life sciences : CMLS · 2026Article
- Prognostic impact of thyroid transcription factor-1 expression and the efficacy of carboplatin plus (nab-) paclitaxel in non-squamous non-small cell lung cancer complicated with idiopathic interstitial pneumonias.Translational lung cancer research · 2026Article
- Hypoxia-induced secretory autophagy in cancer-associated fibroblasts promotes ECM remodelling through serglycin secretion in oral squamous cell carcinoma.Clinical and translational medicine · 2025Article
- Refining treatment strategies for non-small cell lung cancer lacking actionable mutations: insights from multi-omics studies.British journal of cancer · 2025Review
- Single nucleus RNA sequencing unveils relationship between microglia and endothelial cells in mixed Alzheimer's disease and vascular pathology.Neurobiology of disease · 2025Article
- Matrix: a complex amalgam of structures and functions in tumor microenvironment.FEBS open bio · 2025Review
- Nuclear-localized metabolic enzymes: emerging key players in tumor epigenetic regulation.Molecular and cellular biochemistry · 2025Review
- ASO Author Reflections: The Potential of CDO1 as a Key Player in Cancer Biomarkers and Cancer Treatment Strategies.Annals of surgical oncology · 2025Article
- The expression of PD-1 ligands in the immune microenvironment was altered in TTF-1-negative lung adenocarcinoma.Human cell · 2025Article
- Exploring the Role of CDO1 in Breast Cancer: Insights into Tumor Biology and Therapeutic Potential.Annals of surgical oncology · 2025Article
- Genetic drivers of tumor microenvironment and immunotherapy resistance in non-small cell lung cancer: the role ofJournal for immunotherapy of cancer · 2025Review
- TTF-1 expression stratifies chemoimmunotherapy benefits in PD-L1-negative lung adenocarcinoma: a real-world biomarker validation.Journal of thoracic disease · 2025Article
- Mir-494-3p enhances aggressive phenotype of non-small cell lung cancer cells by regulating SET/I2PP2A.Scientific reports · 2025Article
- Diffuse and Strong TTF-1 Expression Predicts Response to Pemetrexed-Based Immunochemotherapy in Advanced Lung Adenocarcinoma.Cancer management and research · 2025Article
- Tumor-Activated Neutrophils Promote Lung Cancer Progression through the IL-8/PD-L1 Pathway.Current cancer drug targets · 2025Article
- Serglycin's role in primary liver cancer: insights into tumor microenvironment and macrophage interaction.Frontiers in immunology · 2025Article
- A strong association between TTF-1 expression and interstitial lung disease in predicting the efficacy of PD-1 inhibitor for nonsquamous NSCLC patients.ERJ open research · 2025Article
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43 authors at 4 institutions in 5 countries.
Funding
Abstract
backgroundApproximately 20% of lung adenocarcinoma (LUAD) is negative for the lineage-specific oncogene Thyroid transcription factor 1 (TTF-1) and exhibits worse clinical outcome with a low frequency of actionable genomic alterations. To identify molecular features associated with TTF-1-negative LUAD, we compared the transcriptomic and proteomic profiles of LUAD cell lines. SRGN , a chondroitin sulfate proteoglycan Serglycin, was identified as a markedly overexpressed gene in TTF-1-negative LUAD. We therefore investigated the roles and regulation of SRGN in TTF-1-negative LUAD.
methodsProteomic and metabolomic analyses of 41 LUAD cell lines were done using mass spectrometry. The function of SRGN was investigated in 3 TTF-1-negative and 4 TTF-1-positive LUAD cell lines and in a syngeneic mouse model (n = 5 to 8 mice per group). Expression of SRGN was evaluated in 94 and 105 surgically resected LUAD tumor specimens using immunohistochemistry. All statistical tests were 2-sided.
resultsSRGN was markedly overexpressed at mRNA and protein levels in TTF-1-negative LUAD cell lines (P < .001 for both mRNA and protein levels). Expression of SRGN in LUAD tumor tissue was associated with poor outcome (hazard ratio = 4.22, 95% confidence interval = 1.12 to 15.86, likelihood ratio test, P = .03), and with higher expression of Programmed cell death 1 ligand 1 (PD-L1) in tumor cells and higher infiltration of Programmed cell death protein 1-positive lymphocytes. SRGN regulated expression of PD-L1 as well as proinflammatory cytokines, including Interleukin-6, Interleukin-8, and C-X-C motif chemokine 1 in LUAD cell lines; increased migratory and invasive properties of LUAD cells and fibroblasts; and enhanced angiogenesis. SRGN was induced by DNA demethylation resulting from Nicotinamide N-methyltransferase-mediated impairment of methionine metabolism.
conclusionsOur findings suggest that SRGN plays a pivotal role in tumor-stromal interaction and reprogramming into an aggressive and immunosuppressive tumor microenvironment in TTF-1-negative LUAD.
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