Hypoxia inducible factor-1α (HIF-1α), induces cytokines such as CXCL8 and tumor dissemination, chemo- and radio-resistance. We analyzed correlation between HIF-1α and CXCL8 levels, tumor characteristics and overall survival in 102 hepatocellular carcinoma (HCC) patients. Levels of HIF-1α and CXCL8 were increased in HCC tissues and cell lines. Patients with high levels of HIF-1α and CXCL8 had worse outcome and poorer prognosis than those with lower levels. Co-overexpression of HIF-1α and CXCL8 was an independent negative prognostic factor for overall and disease-free survival. HIF-1α silencing and CXCL8 siRNA decreased migration under hypoxic conditions in vitro. Hypoxia-induced activation of AKT/mTOR/STAT3 pathways was reversed by depletion of CXCL8. We conclude that HIF-1α and CXCL8 induce HCC progression and metastasis, associated with activation of AKT/mTOR/STAT3. Co-expression of HIF-1α and CXCL8 is a prognostic marker and a potential therapeutic target in HCC.

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BACKGROUNDFocal nodular hyperplasia (FNH) has very low potential risk, and a tendency to spontaneously resolve. Hepatocellular adenoma (HCA) has a certain malignant tendency, and its prognosis is significantly different from FNH. Accurate identification of HCA and FNH is critical for clinical treatment.AIMTo analyze the value of multi-parameter ultrasound index based on logistic regression for the differential diagnosis of HCA and FNH.METHODSThirty-one patients with HCA were included in the HCA group. Fifty patients with FNH were included in the FNH group. The clinical data were collected and recorded in the two groups. Conventional ultrasound, shear wave elastography, and contrast-enhanced ultrasound were performed, and the lesion location, lesion echo, Young’s modulus (YM) value, YM ratio, and changes of time intense curve (TIC) were recorded. Multivariate logistic regression analysis was used to screen the indicators that can be used for the differential diagnosis of HCA and FNH. A ROC curve was established for the potential indicators to analyze the accuracy of the differential diagnosis of HCA and FNH. The value of the combined indicators for distinguishing HCA and FNH were explored.RESULTSMultivariate logistic regression analysis showed that lesion echo (P = 0.000), YM value (P = 0.000) and TIC decreasing slope (P = 0.000) were the potential indicators identifying HCA and FNH. In the ROC curve analysis, the accuracy of the YM value distinguishing HCA and FNH was the highest (AUC = 0.891), which was significantly higher than the AUC of the lesion echo and the TIC decreasing slope (P < 0.05). The accuracy of the combined diagnosis was the highest (AUC = 0.938), which was significantly higher than the AUC of the indicators diagnosing HCA individually (P < 0.05). This sensitivity was 91.23%, and the specificity was 83.33%.CONCLUSIONThe combination of lesion echo, YM value and TIC decreasing slope can accurately differentiate between HCA and FNH.