Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Biosci Rep. 2021 Apr 30;41(4). doi: 10.1042/BSR20210328.
Recent research has indicated that metabolically related genes play crucial roles in the pathogenesis of hepatocellular carcinoma (HCC). We evaluated the associations between novel biomarkers and retinol-binding protein 4 (RBP4) for predicting clinical HCC outcomes, hub-related genes, pathway regulation, and immune cells infiltration. Bioinformatic analyses based on data from The Cancer Genome Atlas were performed using online analysis tools. RBP4 expression was low in HCC and was also down-regulated in pan-cancers compared with normal tissues. RBP4 expression was also significantly different based on age (41-60 years old versus 61-80 years old), and low RBP4 expression levels were associated with advanced tumor stages and grades. Higher RBP4 expression was associated with better overall survival time in HCC patients, and we identified a deletion-mutation rate of 1.4% in RBP4. We also identified ten co-expressed genes most related to RBP4 and explored the relationships between six hub genes (APOB, FGA, FGG, SERPINC1, APOA1, and F2) involved in RBP4 regulation. A pathway enrichment analysis for RBP4 indicated complement and coagulation cascades, metabolic pathways, antibiotic biosynthesis pathways, peroxisome proliferator-activated receptor signaling pathways, and pyruvate metabolism pathways. These results suggest that RBP4 may be a novel biomarker for HCC prognosis, and an indicator of low immune response to the disease.
最近的研究表明，代谢相关基因在肝细胞癌（HCC）的发病机制中起着至关重要的作用。我们评估了新型生物标志物与视黄醇结合蛋白 4（RBP4）在预测 HCC 临床结局、枢纽相关基因、通路调控和免疫细胞浸润方面的相关性。使用在线分析工具对来自癌症基因组图谱的数据分析进行了生物信息学分析。与正常组织相比，RBP4 在 HCC 中表达较低，在泛癌中也下调。RBP4 的表达也因年龄（41-60 岁与 61-80 岁）而显著不同，低 RBP4 表达水平与晚期肿瘤分期和分级相关。RBP4 高表达与 HCC 患者总生存时间较好相关，我们在 RBP4 中发现了 1.4%的缺失突变率。我们还确定了十个与 RBP4 最相关的共表达基因，并探讨了涉及 RBP4 调节的六个枢纽基因（APOB、FGA、FGG、SERPINC1、APOA1 和 F2）之间的关系。RBP4 的通路富集分析表明补体和凝血级联、代谢途径、抗生素生物合成途径、过氧化物酶体增殖物激活受体信号通路和丙酮酸代谢途径。这些结果表明，RBP4 可能是 HCC 预后的新型生物标志物，也是疾病免疫反应低下的指标。
