Lin Tong, Zhang Yingzhao, Lin Zhimei, Peng Lisheng
The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, People's Republic of China.
Department of Science and Education, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, People's Republic of China.
Int J Gen Med. 2021 Oct 30;14:7487-7501. doi: 10.2147/IJGM.S340057. eCollection 2021.
The prognosis of patients with advanced hepatocellular carcinoma (HCC) is still poor, effective therapeutic targets are needed. ZW10 interacting kinetochore protein (Zwint) is an essential component of the mitotic spindle checkpoint and is upregulated in cancers. Disappointing, the role of in HCC has not been fully illuminated.
Multiple tools, including TIMER2.0, Oncomine, GEPIA2, UALCAN, LinkedOmics, Kaplan-Meier Plotter, cBioPortal, and MethSurv, etc. were applied to comprehensively analyze the expression, genetic alternations, clinicopathological relevance, prognostic value, and DNA methylation of , along with its correlations with immune infiltration in HCC. Besides, gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) analysis were performed for the correlated genes of , closely interconnected clusters and hub proteins in the PPI network were discovered to learn the underlying biological mechanisms.
We found was significantly upregulated in diverse cancers including HCC, compared with the corresponding normal controls. upregulation was significantly associated with unfavorable clinicopathological features and survivals of HCC patients. Genetic alternations of frequently occurred, which were linked to worse outcomes of HCC patients. The results of GSEA displayed and its correlated genes might be components of condensed chromosomes and spindles, which participated in biological processes and signaling pathways involving DNA replication, cytokinesis, and cell cycle checkpoint, etc. Three highly interconnected clusters and 10 hub proteins were identified from the PPI network constructed with the correlated genes of . Moreover, expression was found positively correlated with infiltration levels of various immune cells, especially myeloid-derived suppressor cells.
This study demonstrated might be a promising unfavorable prognostic biomarker and a therapeutic target of HCC, which could regulate HCC progression through cell division and immunosuppression.
晚期肝细胞癌（HCC）患者的预后仍然很差，需要有效的治疗靶点。ZW10相互作用的动粒蛋白（Zwint）是有丝分裂纺锤体检查点的重要组成部分，在癌症中上调。令人失望的是，其在HCC中的作用尚未完全阐明。
应用多种工具，包括TIMER2.0、Oncomine、GEPIA2、UALCAN、LinkedOmics、Kaplan-Meier Plotter、cBioPortal和MethSurv等，全面分析Zwint的表达、基因改变、临床病理相关性、预后价值和DNA甲基化，以及其与HCC免疫浸润的相关性。此外，对Zwint的相关基因进行基因集富集分析（GSEA）和蛋白质-蛋白质相互作用（PPI）分析，发现PPI网络中紧密相连的簇和枢纽蛋白，以了解潜在的生物学机制。
我们发现与相应的正常对照相比，Zwint在包括HCC在内的多种癌症中显著上调。Zwint上调与HCC患者不良的临床病理特征和生存率显著相关。Zwint的基因改变频繁发生，这与HCC患者更差的预后相关。GSEA结果显示，Zwint及其相关基因可能是浓缩染色体和纺锤体的组成部分，参与了涉及DNA复制、胞质分裂和细胞周期检查点等生物学过程和信号通路。从用Zwint的相关基因构建的PPI网络中鉴定出三个高度互连的簇和10个枢纽蛋白。此外，发现Zwint表达与各种免疫细胞的浸润水平呈正相关，尤其是髓源性抑制细胞。
本研究表明，Zwint可能是一种有前景的不良预后生物标志物和HCC的治疗靶点，其可通过细胞分裂和免疫抑制调节HCC进展。
