Suzhou Medical College of Soochow University, Suzhou, Jiangsu, China.
Department of General Surgery, The First People's Hospital of Taicang, Taicang Affiliated Hospital of Soochow University, No. 58 Changsheng South Road, Taicang, Suzhou, 215400, Jiangsu, People's Republic of China.
Sci Rep. 2023 Feb 10;13(1):2409. doi: 10.1038/s41598-023-28653-6.
Liver hepatocellular carcinoma (LIHC) is one of the most common malignancies and places a heavy burden on patients worldwide. HAUS augmin-like complex subunit 5 (HAUS5) is involved in the occurrence and development of various cancers. However, the functional role and significance of HAUS5 in LIHC remain unclear. The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO) databases were used to analyze the mRNA expression of HAUS5. The value of HAUS5 in predicting LIHC prognosis and the relationship between HAUS5 and clinicopathological features were assessed by the Kaplan-Meier plotter and UALCAN databases. Functional enrichment analyses and nomogram prediction model construction were performed with the R packages. The LinkedOmics database was searched to reveal co-expressed genes associated with HAUS5. The relationship between HAUS5 expression and immune infiltration was explored by searching the TISIDB database and single-sample gene set enrichment analysis (ssGSEA). The Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (HPA) databases were used to evaluate HAUS5 protein expression. Finally, the effect of HAUS5 on the proliferation of hepatoma cells was verified by CCK-8, colony formation and EdU assays. HAUS5 is aberrantly expressed and associated with a poor prognosis in most tumors, including LIHC. The expression of HAUS5 is significantly correlated with clinicopathological indicators in patients with LIHC. Functional enrichment analysis showed that HAUS5 was closely related to DNA replication, cell cycle and p53 signaling pathway. HAUS5 may serve as an independent risk factor for LIHC prognosis. The nomogram based on HAUS5 had area under the curve (AUC) values of 0.74 and 0.77 for predicting the 3-year and 5-year overall survival (OS) of LIHC patients. Immune correlation analysis showed that HAUS5 was significantly associated with immune infiltration. Finally, the results of in vitro experiments showed that when HAUS5 was knocked down, the proliferation of hepatoma cells was significantly decreased. The pan-oncogene HAUS5 is a positive regulator of LIHC progression and is closely associated with a poor prognosis in LIHC. Moreover, HAUS5 is involved in immune infiltration in LIHC. HAUS5 may be a new prognostic marker and therapeutic target for LIHC patients.
肝细胞肝癌(LIHC)是最常见的恶性肿瘤之一,给全球患者带来了沉重的负担。HAUS augmin-like 复合物亚基 5(HAUS5)参与了各种癌症的发生和发展。然而,HAUS5 在 LIHC 中的功能作用和意义尚不清楚。本研究利用癌症基因组图谱(TCGA)、基因型组织表达(GTEx)、癌症细胞系百科全书(CCLE)和基因表达综合数据库(GEO)分析了 HAUS5 的 mRNA 表达。通过 Kaplan-Meier plotter 和 UALCAN 数据库评估了 HAUS5 预测 LIHC 预后的价值以及 HAUS5 与临床病理特征之间的关系。利用 R 软件包进行功能富集分析和列线图预测模型构建。通过 LinkedOmics 数据库揭示与 HAUS5 相关的共表达基因。通过 TISIDB 数据库和单样本基因集富集分析(ssGSEA)探索 HAUS5 表达与免疫浸润的关系。利用临床蛋白质肿瘤分析联盟(CPTAC)和人类蛋白质图谱(HPA)数据库评估 HAUS5 蛋白表达。最后,通过 CCK-8、集落形成和 EdU 实验验证了 HAUS5 对肝癌细胞增殖的影响。HAUS5 在大多数肿瘤中异常表达,并与不良预后相关,包括 LIHC。HAUS5 的表达与 LIHC 患者的临床病理指标显著相关。功能富集分析表明,HAUS5 与 DNA 复制、细胞周期和 p53 信号通路密切相关。HAUS5 可能是 LIHC 预后的独立危险因素。基于 HAUS5 的列线图预测 LIHC 患者 3 年和 5 年总生存率(OS)的 AUC 值分别为 0.74 和 0.77。免疫相关性分析表明,HAUS5 与免疫浸润显著相关。最后,体外实验结果表明,当 HAUS5 被敲低时,肝癌细胞的增殖明显减少。泛癌基因 HAUS5 是 LIHC 进展的正调节剂,与 LIHC 预后不良密切相关。此外,HAUS5 参与了 LIHC 中的免疫浸润。HAUS5 可能成为 LIHC 患者新的预后标志物和治疗靶点。