Wan Shunyuan, Pan Qi, Yang Guang, Kuang Jing, Luo Shiqiao
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
Department of Dermatology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400011, P.R. China.
Oncol Lett. 2020 Oct;20(4):13. doi: 10.3892/ol.2020.11874. Epub 2020 Jul 15.
Hepatocellular carcinoma (HCC) is one of the most prevalent types of cancer worldwide. The present study attempted to identify a prognostic biomarker for HCC. RNA sequencing data from the GSE63863 dataset were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified based on a protein-protein interaction (PPI) network, and prognostic evaluation was subsequently conducted. Following lentiviral transfection, the migratory, proliferative and apoptotic abilities of cells were evaluated using wound healing, Cell Counting Kit-8, Transwell migration and apoptosis assays. A total of 192 DEGs were identified from 11 pairs of HCC and matched non-tumor samples. The PPI network revealed the top three modules, and eight genes were identified from these modules. The expression levels of cytochrome P450 family 4 subfamily F member 2 (CYP4F2) were downregulated in 50 HCC samples from The Cancer Genome Atlas and in the HCC Hep3B cell line. Low CYP4F2 expression was associated with a lower overall survival time. Functional studies revealed that CYP4F2 overexpression inhibited HCC cell proliferation and migration, and induced apoptosis. Furthermore, CYP4F2 overexpression repressed the expression of genes in the nuclear factor, erythroid 2 like 2 (Nrf2) signaling pathway, including Nrf2, heme oxygenase-1 and ferritin heavy chain 1, while increasing NAD(P)H quinone dehydrogenase 1 expression, suggesting that CYP4F2 overexpression reversed the antioxidant response of liver cancer cells. Overall, the present findings indicated that CYP4F2 may be a potential prognostic biomarker for predicting tumorigenesis and long-term survival rates in patients with HCC.
肝细胞癌（HCC）是全球最常见的癌症类型之一。本研究试图鉴定一种HCC的预后生物标志物。从基因表达综合数据库下载了来自GSE63863数据集的RNA测序数据。基于蛋白质-蛋白质相互作用（PPI）网络鉴定差异表达基因（DEG），随后进行预后评估。慢病毒转染后，使用伤口愈合、细胞计数试剂盒-8、Transwell迁移和凋亡检测评估细胞的迁移、增殖和凋亡能力。从11对HCC和匹配的非肿瘤样本中总共鉴定出192个DEG。PPI网络揭示了前三个模块，并从这些模块中鉴定出八个基因。细胞色素P450家族4亚家族F成员2（CYP4F2）在来自癌症基因组图谱的50个HCC样本和HCC Hep3B细胞系中的表达水平下调。低CYP4F2表达与较低的总生存时间相关。功能研究表明，CYP4F2过表达抑制HCC细胞增殖和迁移，并诱导凋亡。此外，CYP4F2过表达抑制核因子红细胞2样2（Nrf2）信号通路中的基因表达，包括Nrf2、血红素加氧酶-1和铁蛋白重链1，同时增加NAD（P）H醌脱氢酶1的表达，表明CYP4F2过表达逆转了肝癌细胞的抗氧化反应。总体而言，本研究结果表明，CYP4F2可能是预测HCC患者肿瘤发生和长期生存率的潜在预后生物标志物。
