Department of Clinical Laboratory, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Clinical Laboratory, Guangxi International Zhuang Medicine Hospital, Nanning, 530201 Guangxi, China.
Oxid Med Cell Longev. 2022 Sep 19;2022:8421813. doi: 10.1155/2022/8421813. eCollection 2022.
The specificity and sensitivity of hepatocellular carcinoma (HCC) diagnostic markers are limited, hindering the early diagnosis and treatment of HCC patients. Therefore, improving prognostic biomarkers for patients with HCC is urgently needed.
HCC-related datasets were downloaded from the public databases. Differentially expressed genes (DEGs) between HCC and adjacent nontumor liver tissues were then identified. Moreover, the intersection of DEGs in four datasets (GSE138178, GSE77509, GSE84006, and TCGA) was used in the functional enrichment, and module genes were obtained by a coexpression network. Cox and Kaplan-Meier analyses were used to identify overall survival- (OS-) related genes from module genes. Area under the curve (AUC) > 0.9 of OS-related genes was then carried out in order to perform the protein-protein interaction network. The feature genes were identified by least absolute shrinkage and selection operator (LASSO). Furthermore, the hub gene was identified through the univariate Cox model, after which the correlation analysis between the hub gene and pathways was explored. Finally, infiltration in immune cell types in HCC was analyzed.
A total of 2,227 upregulated genes and 1,501 downregulated DEGs were obtained in all four datasets, which were mainly found to be involved in the cell cycle and retinol metabolism. Accordingly, 998 OS-related genes were screened to construct the LASSO model. Finally, 8 feature genes (BUB1, CCNB1, CCNB2, CCNA2, AURKB, CDC20, OIP5, and TTK) were obtained. CDC20 was shown to serve as a poor prognostic gene in HCC and was mainly involved in the cell cycle. Moreover, a positive correlation was noted between the high degree of infiltration with Th2 and CDC20.
High expression of CDC20 predicted poor survival, as potential target in the treatment for HCC.
肝细胞癌(HCC)诊断标志物的特异性和敏感性有限,这阻碍了 HCC 患者的早期诊断和治疗。因此,迫切需要改善 HCC 患者的预后生物标志物。
从公共数据库中下载 HCC 相关数据集。然后鉴定 HCC 与相邻非肿瘤肝组织之间的差异表达基因(DEG)。此外,四个数据集(GSE138178、GSE77509、GSE84006 和 TCGA)中 DEG 的交集用于功能富集,并通过共表达网络获得模块基因。Cox 和 Kaplan-Meier 分析用于从模块基因中识别与总生存期(OS)相关的基因。然后对 OS 相关基因的 AUC>0.9 进行蛋白质-蛋白质相互作用网络。通过最小绝对值收缩和选择算子(LASSO)识别特征基因。此外,通过单变量 Cox 模型识别枢纽基因,之后探讨枢纽基因与途径之间的相关性。最后,分析 HCC 中免疫细胞类型的浸润情况。
在所有四个数据集中共获得 2227 个上调基因和 1501 个下调 DEG,它们主要与细胞周期和视黄醇代谢有关。因此,筛选了 998 个 OS 相关基因来构建 LASSO 模型。最后,获得了 8 个特征基因(BUB1、CCNB1、CCNB2、CCNA2、AURKB、CDC20、OIP5 和 TTK)。CDC20 被证明是 HCC 中的不良预后基因,主要参与细胞周期。此外,还观察到高浸润度 Th2 与 CDC20 之间存在正相关。
CDC20 的高表达预示着预后不良,可能成为 HCC 治疗的潜在靶点。