下调和上调
医学
音猬因子
肝细胞癌
癌症研究
生物标志物
缺氧(环境)
内科学
肿瘤科
生物
信号转导
基因
生物化学
有机化学
化学
氧气
作者
Jiali Zhao,Guifang Zeng,Emily Lin,Chaonong Cai,Peiping Li,Baojia Zou,Jian Li
标识
DOI:10.1080/08941939.2022.2090034
摘要
Background Hypoxia-inducible factor-1α (HIF-1α) or sonic hedgehog (SHH) is associated with hepatocellular carcinoma (HCC) progression. Hypoxia inhibits ferroptosis, which induces cancer cell death. However, the correlation between the combined HIF-1α and SHH up-regulation with prognosis, and the association between SHH and ferroptosis remain unclear. This study aimed to investigate them.Methods We detected the expression of HIF-1α and SHH in HCC. Cox regression, clinical data, and Kaplan–Meier analyses were performed. In vitro cell experiments verified the relationship between HIF-1α and SHH, and observed the invasion of hypoxic HCC cells. The correlation between SHH and ferroptosis was also analyzed.Results HIF-1α and SHH expression levels were significantly correlated with HCC (p < 0.0001). HIF-1α and SHH expression levels were found to be associated with TNM stage (p = 0.0121, p = 0.0078, respectively), vascular invasion (p < 0.0001, p < 0.0001, respectively), and recurrence (p = 0.0212, p = 0.0392, respectively). The combined upregulation of HIF-1α and SHH was an independent factor for predicting the overall survival (OS) of patients with HCC (p = 0.003), who had the shortest OS (p = 0.0009). SHH paralleled the increase in HIF-1α expression, which promotes cancer cell invasion. The upregulation of SHH was related to the inhibition of the expression of ferroptosis-related factors (FANCD2, p < 0.0001 and FTH1, p = 0.0009) in HCC.Conclusion Combined HIF-1α and SHH upregulation is a potentially poor prognosis indicator in patients with HCC because the upregulation of SHH inhibits ferroptosis in hypoxic cancer cells.
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