ArticleBMC cancer2014
High STAT1 mRNA levels but not its tyrosine phosphorylation are associated with macrophage infiltration and bad prognosis in breast cancer.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
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Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Clinicopathological and prognostic significance of programmed cell death ligand 1 expression in patients diagnosed with breast cancer: meta-analysis.The British journal of surgery · 2021Pooled it
- Pooled it
- JAK/STAT1-interferon-ISGylation networks in breast cancer resistance to inhibitors of FOXM1 and CDK4/6.NPJ breast cancer · 2026Article
- Hepatic Recurrence Rate Based on Extent of Adjuvant Floxuridine Exposure After Resection of Colorectal Liver Metastases.Annals of surgical oncology · 2026Article
- Age-related and postmenopausal breast cancer progression and treatment management: The significance of pro-inflammatory cytokines and CXC chemokines.Genes & diseases · 2025Review
- Chalcone-9: a novel inhibitor of the JAK-STAT pathway with potent anti-cancer effects in triple-negative breast cancer cells.Pharmacological reports : PR · 2025Article
- Assessment of Cytotoxicity, Impact on Cell Migration and Apoptotic Modulation of Acteoside and Plantamajoside on Human Breast Adenocarcinoma (MCF-7).Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Tp53 determines the spatial dynamics of M1/M2 tumor-associated macrophages and M1-driven tumoricidal effects.Cell death & disease · 2025Article
- Unveiling the power of Treg.Sig: a novel machine-learning derived signature for predicting ICI response in melanoma.Frontiers in immunology · 2025Article
- Senomorphic activity of a combination of niacinamide and hyaluronic acid: correlation with clinical improvement of skin aging.Scientific reports · 2024Article
- Upregulated SPAG6 correlates with increased STAT1 and is associated with reduced sensitivity of interferon-α response in BCR::ABL1 negative myeloproliferative neoplasms.Cancer science · 2023Article
- High-Dose Paclitaxel and its Combination with CSF1R Inhibitor in Polymeric Micelles for Chemoimmunotherapy of Triple Negative Breast Cancer.Nano today · 2023Article
- G6PD activation in TNBC cells induces macrophage recruitment and M2 polarization to promote tumor progression.Cellular and molecular life sciences : CMLS · 2023Article
- The predictive value of prognosis and therapeutic response for STAT family in pancreatic cancer.Heliyon · 2023Article
- An Isoxazoloquinone Derivative Inhibits Tumor Growth by Targeting STAT3 and Triggering Its Ubiquitin-Dependent Degradation.Cancers · 2023Article
- Dysregulation in IFN-γ signaling and response: the barricade to tumor immunotherapy.Frontiers in immunology · 2023Review
- Tumor-associated macrophages: an effective player of the tumor microenvironment.Frontiers in immunology · 2023Review
- Article
- The Pharmacologically Active Alkaloid Cryptolepine Activates a Type 1 Interferon Response That Is Independent of MAVS and STING Pathways.Journal of immunology research · 2022Article
- Activation of the IFN Signaling Pathway is Associated with Resistance to CDK4/6 Inhibitors and Immune Checkpoint Activation in ER-Positive Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundSTAT1 has been attributed a function as tumor suppressor. However, in breast cancer data from microarray analysis indicated a predictive value of high mRNA expression levels of STAT1 and STAT1 target genes belonging to the interferon-related signature for a poor response to therapy. To clarify this issue we have determined STAT1 expression levels and activation by different methods, and investigated their association with tumor infiltration by immune cells. Additionally, we evaluated the interrelationship of these parameters and their significance for predicting disease outcome.
methodsExpression of STAT1, its target genes SOCS1, IRF1, CXCL9, CXCL10, CXCL11, IFIT1, IFITM1, MX1 and genes characteristic for immune cell infiltration (CD68, CD163, PD-L1, PD-L2, PD-1, CD45, IFN-γ, FOXP3) was determined by RT-PCR in two independent cohorts comprising 132 breast cancer patients. For a subset of patients, protein levels of total as well as serine and tyrosine-phosphorylated STAT1 were ascertained by immunohistochemistry or immunoblotting and protein levels of CXCL10 by ELISA.
resultsmRNA expression levels of STAT1 and STAT1 target genes, as well as protein levels of total and serine-phosphorylated STAT1 correlated with each other in neoplastic tissue. However, there was no association between tumor levels of STAT1 mRNA and tyrosine-phosphorylated STAT1 and between CXCL10 serum levels and CXCL10 expression in the tumor. Tumors with increased STAT1 mRNA amounts exhibited elevated expression of genes characteristic for tumor-associated macrophages and immunosuppressive T lymphocytes. Survival analysis revealed an association of high STAT1 mRNA levels and bad prognosis in both cohorts. A similar prognostically relevant correlation with unfavorable outcome was evident for CXCL10, MX1, CD68, CD163, IFN-γ, and PD-L2 expression in at least one collective. By contrast, activation of STAT1 as assessed by the level of STAT1-Y701 phosphorylation was linked to positive outcome. In multivariate Cox regression, the predictive power of STAT1 mRNA expression was lost when including expression of CXCL10, MX1 and CD68 as confounders.
conclusionsOur study confirms distinct prognostic relevance of STAT1 expression levels and STAT1 tyrosine phosphorylation in breast cancer patients and identifies an association of high STAT1 levels with elevated expression of STAT1 target genes and markers for infiltrating immune cells.
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