Guizhou Provincial Key Laboratory of Pathogenesis & Drug Research on Common Chronic Diseases, Department of Physiology, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, China.
State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.
Bioengineered. 2022 May;13(5):12193-12210. doi: 10.1080/21655979.2022.2073943.
Hypoxia environment exists in already started hepatocellular carcinoma (HCC) and promotes its progression by driving changes in the gene expression profiles of cells. However, the status of hypoxia-driven genes in HCC is largely unknown. In the present study, 368 HCC tissues from The Cancer Genome Atlas were divided into high and low hypoxia groups according to their hypoxia signatures. A total of 1,142 differentially expressed genes (DEGs) were identified between the two groups, and 34 of these DEGs were highly expressed in HCC tissues compared with adjacent tissues, especially in HCC tissues from patients with stage III-IV HCC. After constructing a protein-protein interaction network and applying the least absolute shrinkage and selection operator Cox regression method for 34 DEGs, a three-gene signature (complement factor H related 3 [], egl-9 family hypoxia inducible factor 3 [], and chromogranin A []) was constructed and had prognostic value to predicted outcome of patients with HCC. This three-gene signature was suitable for classifying patients with HCC in the International Cancer Genome Consortium. CFHR3 shows remarkable diagnostic value in HCC. Hypoxia decreased CFHR3 expression, but increased HCC cell proliferation and motility. Overexpression of CFHR3 in HCC cells under hypoxia reversed the stimulatory effects of hypoxia and suppressed cell proliferation and metastasis . In conclusion, we identified a novel hypoxia-driven gene signature (, and ) for reliable prognostic prediction of HCC, and demonstrated that overexpression of CFHR3 may be a potential strategy to overcome hypoxia and treat HCC.
缺氧环境存在于已经发生的肝细胞癌（HCC）中，并通过驱动细胞基因表达谱的变化来促进其进展。然而，HCC 中缺氧驱动基因的状态在很大程度上是未知的。在本研究中，根据缺氧特征将来自癌症基因组图谱的 368 例 HCC 组织分为高和低缺氧组。两组间共鉴定出 1142 个差异表达基因（DEGs），其中 34 个 DEGs在 HCC 组织中与相邻组织相比高表达，尤其是在 III-IV 期 HCC 患者的 HCC 组织中。构建蛋白质-蛋白质相互作用网络并应用最小绝对收缩和选择算子 Cox 回归方法对 34 个 DEGs 进行分析后，构建了一个由三个基因组成的特征基因（补体因子 H 相关蛋白 3[ ], egl-9 家族缺氧诱导因子 3[ ], 和嗜铬粒蛋白 A[ ]），并具有预测 HCC 患者预后的价值。该三基因特征适用于国际癌症基因组联盟的 HCC 患者分类。CFHR3 在 HCC 中具有显著的诊断价值。缺氧降低 CFHR3 的表达，但增加 HCC 细胞的增殖和迁移。在缺氧条件下过表达 CFHR3 可逆转缺氧的刺激作用，并抑制细胞增殖和转移。总之，我们确定了一个新的缺氧驱动基因特征（, 和 ），用于 HCC 的可靠预后预测，并表明 CFHR3 的过表达可能是克服缺氧和治疗 HCC 的潜在策略。
