ArticlePloS one2013
Dysfunctional activation of neurotensin/IL-8 pathway in hepatocellular carcinoma is associated with increased inflammatory response in microenvironment, more epithelial mesenchymal transition in cancer and worse prognosis in patients.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Pretreatment of UC-MSCs with IFN-α2 improves treatment of liver fibrosis by recruiting neutrophils.Journal of translational medicine · 2023Article
- Tumor cell density dependent IL-8 secretion induces the fluctuation of tregs/CD8 + T cells infiltration in hepatocellular carcinoma: one prompt for the existence of density checkpoint.Journal of translational medicine · 2023Article
- Effect of IL-8 on hepatocellular carcinoma-associated metastasis by targeting MMP9 in mice.Translational cancer research · 2022Article
- New Insights in the Control of Fat Homeostasis: The Role of Neurotensin.International journal of molecular sciences · 2022Review
- Roles of the CXCL8-CXCR1/2 Axis in the Tumor Microenvironment and Immunotherapy.Molecules (Basel, Switzerland) · 2021Review
- Risk characteristics with seven epithelial-mesenchymal transition-related genes are used to predict the prognosis of patients with hepatocellular carcinoma.Journal of gastrointestinal oncology · 2021Article
- Interleukin-8: A chemokine at the intersection of cancer plasticity, angiogenesis, and immune suppression.Pharmacology & therapeutics · 2021Review
- Neurotensin pathway in digestive cancers and clinical applications: an overview.Cell death & disease · 2020Review
- Generation of onco-enhancer enhances chromosomal remodeling and accelerates tumorigenesis.Nucleic acids research · 2020Article
- Article
- The role of Neurotensin and its receptors in non-gastrointestinal cancers: a review.Cell communication and signaling : CCS · 2020Review
- Relationship between epithelial-to-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2018Review
- Validation of Neurotensin Receptor 1 as a Therapeutic Target for Gastric Cancer.Molecules and cells · 2018Article
- Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative-intent surgery for hepatocellular carcinoma: experience from a developing country.Cancer management and research · 2018Article
- Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis.Oncology letters · 2017Article
- Article
- Sohlh2 suppresses epithelial to mesenchymal transition in breast cancer via downregulation of IL-8.Oncotarget · 2016Article
- Evaluation and characterization of anti-RalA autoantibody as a potential serum biomarker in human prostate cancer.Oncotarget · 2016Article
- Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC.Scientific reports · 2016Article
- Tumor-associated antigen CAPERα and microvessel density in hepatocellular carcinoma.Oncotarget · 2016Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the role of neurotensin (NTS) in hepatocellular carcinoma (HCC) sub- grouping and the clinical and pathological significance of activation of NTS/IL-8 pathway in HCC.
methodsThe genome-wide gene expression profiling were conducted in 10 pairs of cancer tissues and corresponding normal adjacent tissues samples using Affymetrix GeneChip® Human Genome U133 Plus 2.0 microarray to screen differentially expressing genes and enrich dysfunctional activated pathways among different HCC subgroups. The levels of NTS protein and multiple inflammation and epithelial mesenchymal transition (EMT) related proteins, including IL-8, VEGF, MMP9, CD68, E-Cadherin, β-Catenin and Vimentin were examined in 64 cases of paraffin-embedded HCC samples using immunohistochemistry (IHC) staining method. The clinical outcome and overall survival (OS) were compared.
resultsA subgroup of HCC characterized by up-regulated NTS expression was accompanied by up-regulated inflammatory responses and EMT. The direct interaction between NTS and IL-8 was identified by pathway enrichment analysis. Significantly increased IL-8 protein was confirmed in 90.91% of NTS(+) HCC samples and significantly positively correlated to the levels of NTS protein in cancer tissues (P = 0.036), which implied activation of NTS/IL-8 pathway in HCC. The levels of VEGF and MMP9 correlated with co-expression of NTS and IL-8. Increased infiltration of CD68(+) macrophages and more cancer cells displaying EMT features were found in NTS(+)IL-8(+) samples. The co-expression of NTS and IL-8 in cancer significantly correlated with the clinical outcomes, as the mortality rate of NTS(+)IL-8(+) HCC patients is 2.5-fold higher than the others after the surgery (P = 0.022). Accordingly, the OS of NTS(+)IL-8(+) HCC patients significantly decreased who are under a higher hazard of death at an expected hazard ratio (HR) of 3.457.
conclusionDysfunctional activation of the NTS/IL-8 pathway was detected in HCC which is associated with increased inflammatory response in microenvironment, enhanced EMT in cancer, and worse prognosis in HCC patients.
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