Background The study examines the expression and function of hypoxia-inducible gene 2 (HIG2) in hepatocellular carcinoma (HCC) tissues and cells. Methods Forty patients with HCC were included in the study. Bioinformatic analysis was used to analyze the clinical relevance of HIG2 expression in HCC tissue samples. Immunohistochemistry was employed to determine the expression of target proteins in tumor tissues. Hepatic HepG2 and SMMC-7721 cells were transfected with HIG2 -targeting siRNA with Lipofectamine 2000. qRT-PCR was carried out to determine gene expression levels, while Western blotting was used to determine protein expression. A CCK-8 assay was performed to detect proliferation of cells, while migration and invasion of cells were studied by Transwell assay. Flow cytometry was carried out to detect surface markers and effector molecules in Nature killercells, as well as the killing effect of NK cells. Results HIG2 expression was upregulated in HCC. Silencing of HIG2 suppressed HCC cell migration and invasion. The killing effect of NK cells on HCC cells was enhanced after HIG2 was silenced in HCC cells. Conditioned media from HIG2 -silenced SMMC-7721 cells inhibited the phenotype and function of NK cells. HCC cells with silenced expression of HIG2 modulated the activity of NK cells via STAT3. HIG2 promoted the evasion of HCC cells from killing by NK cells through upregulation of IL-10 expression. Conclusion The study demonstrates that HIG2 activates the STAT3 signaling pathway in NK cells by promoting IL-10 release by HCC cells, thereby inhibiting the killing activity of NK cells, and subsequently promoting the recurrence and metastasis of HCC.

BackgroundThis study investigated the effect of supernatant of endothelial cells stimulated by peripheral blood serum from sepsis patients on phenotype and function of peripheral NKT cells.Material/MethodsTwenty-one patients with sepsis and 21 healthy subjects were included. Peripheral blood (5 ml) was collected from all patients and healthy subjects. To isolate peripheral blood mononuclear cells (PBMCs), Ficoll lymphocyte separation solution was used. Flow cytometry was carried out to determine NKT cell ratio, activity, and cytokine secretion. Human umbilical vein endothelial cells were cultured with serum from sepsis patients for 48 h before changing to fresh medium, and supernatant was collected. The supernatant was used to co-culture PBMCs before analyzing NKT activity and cytokines.ResultsThe ratios of CD3-CD56+NK cells and CD3+CD56+NKT cells were increased in peripheral blood from sepsis patients. Surface receptors p30, G2D, and p44 of CD3+CD56+NKT cells were elevated, while inhibitory receptors NKG2A and 158b were decreased. CD4+ NKT cells in peripheral blood from sepsis patients were enhanced. GranB, IFN-γ, IL-4, and IL-17 in NKT cells from sepsis patients were up-regulated. After co-culture with vascular endothelial cells treated with sepsis serum, expression of p30 and G2D in NKT cells was upregulated, and number of TCRVα24-positive cells was increased. In addition, ratio of CD4+NKT cells was increased, and intracellular expression of IL-4 and IFN-γ was elevated.ConclusionsThe study demonstrates that the level of NKT cells in peripheral blood from sepsis patients is increased, and their activity is enhanced. In addition, vascular endothelial cells from sepsis patients can regulate the activity of NKT cells.

BackgroundThe current study aims at using the whole genome expression profile chips for systematically investigating the diagnostic and prognostic values of excision repair cross-complementation (ERCC) genes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Materials and methodsWhole genome expression profile chips were obtained from the GSE14520. The receiver-operating characteristic (ROC) curve, survival analysis, and nomogram were used to investigate the diagnostic and prognostic values of ERCC genes. Investigation of the potential function of ERCC8 was carried out by gene set enrichment analysis (GSEA) and genome-wide coexpression analysis.ResultsROC analysis suggests that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated and may have potential to distinguish between HBV-related HCC tumor and paracancerous tissues (area under the curve of ROC ranged from 0.623 to 0.744). Survival analysis demonstrated that high ERCC8 expression was associated with a significantly decreased risk of recurrence (adjusted P=0.021; HR=0.643; 95% CI=0.442–0.937) and death (adjusted P=0.049; HR=0.631; 95% CI=0.399–0.998) in HBV-related HCC. Then, we also developed two nomograms for the HBV-related HCC individualized prognosis predictions. GSEA suggests that the high expression of ERCC8 may have involvement in the energy metabolism biological processes. As the genome-wide coexpression analysis and functional assessment of ERCC8 suggest, those coexpressed genes were significantly enriched in multiple biological processes of DNA damage and repair.ConclusionThe present study indicates that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated between HBV-related HCC tumor and paracancerous tissues and that the mRNA expression of ERCC8 may serve as a potential biomarker for the HBV-related HCC prognosis.

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