ArticleWorld journal of gastroenterology2015
Decreased STAT4 indicates poor prognosis and enhanced cell proliferation in hepatocellular carcinoma.
Article in World journal of gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 44 citations in OpenAlex.
- Effects of β‑hydroxybutyrate on restoring autophagic flux and mitochondrial function in macrophages exposed to oxidized low‑density lipoprotein.Molecular medicine reports · 2026Article
- GNL3L-LMNB1 signaling axis promotes lung squamous cell carcinoma growth and ferroptosis resistance via NF-κB activation.Journal of thoracic disease · 2026Article
- PSAT1 regulated by STAT4 enhances the proliferation, invasion and migration of ovarian cancer cells via the PI3K/AKT pathway.International journal of molecular medicine · 2025Article
- Mechanisms and therapeutic prospect of the JAK-STAT signaling pathway in liver cancer.Molecular and cellular biochemistry · 2025Review
- Effects of STAT4 on myocardial ischemia‑reperfusion injury and the underlying mechanisms.Molecular medicine reports · 2024Article
- Identification and validation of STAT4 as a prognostic biomarker in acute myeloid leukemia.Bioscience reports · 2024Article
- High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression.Open medicine (Warsaw, Poland) · 2024Article
- Interplay between signal transducers and activators of transcription (STAT) proteins and cancer: involvement, therapeutic and prognostic perspective.Clinical and experimental medicine · 2023Review
- STAT4 facilitates PD-L1 level via IL-12R/JAK2/STAT3 axis and predicts immunotherapy response in breast cancer.MedComm · 2023Article
- Assessment of STAT4 Variants and Risk of Hepatocellular Carcinoma in Latin Americans and Europeans.Cancers · 2023Article
- Article
- The miR-141/200c-STAT4 Axis Contributes to Leukemogenesis by Enhancing Cell Proliferation in T-PLL.Cancers · 2023Article
- Characterization of Lactate Metabolism Score in Breast and Thyroid Cancers to Assist Immunotherapy via Large-Scale Transcriptomic Data Analysis.Frontiers in pharmacology · 2022Article
- Type 1 T Helper Cell-Based Molecular Subtypes and Signature Are Associated with Clinical Outcome in Pancreatic Ductal Adenocarcinoma.Frontiers in cell and developmental biology · 2022Article
- A Case of Rapidly Progressing Hepatocellular Carcinoma after Administration of JAK Inhibitors to Treat Rheumatoid Arthritis.Case reports in rheumatology · 2022Article
- MiR-363-5p modulates regulatory T cells through STAT4-HSPB1-Notch1 axis and is associated with the immunological abnormality in Graves' disease.Journal of cellular and molecular medicine · 2021Article
- Impact of STAT Proteins in Tumor Progress and Therapy Resistance in Advanced and Metastasized Prostate Cancer.Cancers · 2021Review
- Development and verification of an immune-related gene pairs prognostic signature in ovarian cancer.Journal of cellular and molecular medicine · 2021Article
- Genetic variants in STAT4 and their interactions with environmental factors for the incidence of hepatocellular carcinoma.Cancer biomarkers : section A of Disease markers · 2021Article
- A Reliable Prognostic Model for HCC Using Histological Grades and the Expression Levels of Related Genes.Journal of oncology · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimTo investigate the role of signal transduction and activation of transcription 4 (STAT4) in the development and progression of human hepatocellular carcinoma (HCC).
methodsRecent genetic investigations have identified that a genetic variant of STAT4 is associated with hepatitis B virus (HBV)-related HCC. The level of STAT4 in 90 HCC patients was examined via Western blot and immunohistochemical analyses. The correlation between STAT4 expression and the clinicopathological characteristics of the patients was analyzed. The level of STAT4 expression in the HCC liver tissues was significantly lower than that in the non-HCC liver tissues and correlated with tumor size, histological grade of HCC and serum hepatitis B surface antigen level in HCC patients. The data were statistically analyzed using SPSS. Furthermore, siRNA oligos targeting STAT4 were employed to investigate the influence of STAT4 RNA interference on HCC cell physiology. Based on Cell Counting Kit-8 and flow cytometric assays, we found that depletion of STAT4 expression significantly enhanced the proliferation of L02 cells.
resultsSTAT4 protein expression was significantly lower in HCC tissues than in normal liver tissues. Immunohistochemistry followed by statistical analysis revealed that the expression of STAT4 negatively correlated with Ki67 expression (r = 0.851; P < 0.05) and positively correlated with maximal tumor size (P < 0.05), HBV (P = 0.012) and histological grade (P < 0.05). Kaplan-Meier analysis revealed significant differences in the survival curves between HCC patients expressing low and high levels of STAT4 and Ki67 (P < 0.05). Based on a multivariate Cox proportional hazard model, STAT4 expression was an independent prognostic indicator for HCC patients who underwent curative resection. In vitro, following the release of L02 cell lines from serum starvation, the expression of STAT4 was downregulated, and transfection of L02 cells with siRNA targeting STAT4 inhibited cell proliferation.
conclusionOur data indicate that STAT4 may inhibit HCC development by modulating HCC cell proliferation.
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