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Predictive value of intratumour inflammatory cytokine mRNA levels of hepatocellular carcinoma patients and activation of two distinct pathways govern IL-8 induced epithelial-mesenchymal transition in human hepatic cancer cell lines. | LitMetric

AI Article Synopsis

  • - Hepatocellular carcinoma (HCC) is linked to persistent liver inflammation, which may promote cancer development, but the role of inflammatory cytokines within the tumor is not well understood.
  • - The study identified IL-8 as a critical cytokine connected to poor survival outcomes in HCC patients, finding that low IL-8 levels correlate with less invasive disease and better overall survival.
  • - Experimental results indicate that IL-8 enhances the migration and invasion of liver cancer cells by triggering epithelial-mesenchymal transition (EMT) through specific signaling pathways, highlighting its potential as a target for liver cancer therapy.

Article Abstract

Hepatocellular carcinoma (HCC) is always accompanied by persistent inflammation of liver tissues, which is considered to exert protumourigenic effects by promoting cancer growth, progression, and metastasis. However, the tumour-promoting roles and predictive value of intratumoural inflammatory cytokines remain unclear. In the present study, we used database analysis, clinical pathological studies, and in vitro biological experiments on human hepatic cancer cell lines to assess the prognostic potential of the primary tumour cytokine mRNA levels and underlying mechanisms in HCC. First, we assessed the prognostic value of several cytokines from the TCGA database and found that IL-8 is a unique cytokine that is associated with poor overall survival of HCC patients. Then, we collected 87 HCC tumour and adjacent non-tumour specimens from patients and confirmed that patients with low IL-8 expression exhibited less intrahepatic invasion or distant metastasis, a lower recurrence rate and longer overall survival time compared to patients with high IL-8 expression. Wound healing, transwell, and western blotting assay results showed that IL-8 promotes the migration and invasion of Huh-7 and HepG2 cells, and the underlying mechanism is that IL-8 induces the EMT of HCC cells via the IL-8/ERK1/2/SNAI1 and IL-8/STAT3/TWIST1 signalling pathways. These results provide valuable biological IL-8 information which needs to be further investigated in liver cancer target therapy research. Furthermore, the intratumoural cytokine expression at the mRNA level may provide insight into hepatocarcinoma prognosis.

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Source
http://dx.doi.org/10.1016/j.cyto.2019.03.012DOI Listing

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