关键词: CKS2 hepatocellular carcinoma immune cycle immune markers immunomodulators tumor immune microenvironment

来  源:   DOI:10.2147/JHC.S427624   PDF(Pubmed)

Abstract:
UNASSIGNED: Cyclin-dependent kinase regulatory subunit 2 (CKS2) has an important function in regulating cancer progression and cell cycle. This research aims to ascertain how CKS2 plays its part through multi-omics analyses, to reveal its relationship with the immune microenvironment in hepatocellular carcinoma (HCC).
UNASSIGNED: Multiple databases were used to determine the transcriptional data of CKS2, epigenetic changes, and effects thereof upon the prognosis of HCC patients. The biological functions of CKS2 in HCC were expounded by functional enrichment analysis. TIMER, GSEA, TIP, and online single-cell sequencing databases were adopted for revealing correlations of CKS2 expression with infiltration of immune cells, immunomodulators, immunity cycle, and immune markers in the immune microenvironment of HCC. In addition, qRT-PCR and Western blot were used to validate gene expression in tissues from HCC patients.
UNASSIGNED: Open database analysis confirmed that CKS2 is highly expressed in HCC and that it is related to poor prognosis in HCC patients. Aberrant methylation levels of the two methylation sites of CKS2 in HCC contributed to its high expression and were correlated significantly with survival. The CKS2 expression was positively correlated with most immunomodulators and infiltration levels for B and CD8+T cells, dendritic cells, and macrophages, especially exhausted CD8+T cells. Besides, the CKS2 expression was also found to have significant correlations with immunity cycle steps and diverse immune markers in HCC. The high CKS2 expression was confirmed in HCC at both mRNA and protein levels, showing a significant increase compared to normal tissue.
UNASSIGNED: CKS2 is a potential prognostic biomarker of HCC and can promote the progression of HCC via its influences on the immune environment. Additionally, a positive correlation between CKS2 and immune markers was observed, highlighting its potential as an immunotherapeutic target.
摘要:
细胞周期蛋白依赖性激酶调节亚基2(CKS2)在调节癌症进展和细胞周期方面具有重要功能。本研究旨在确定CKS2如何通过多组学分析发挥作用,揭示其与肝细胞癌(HCC)免疫微环境的关系。
使用多个数据库来确定CKS2的转录数据,表观遗传变化,及其对HCC患者预后的影响。通过功能富集分析阐述了CKS2在HCC中的生物学功能。TIMER,GSEA,提示,和在线单细胞测序数据库用于揭示CKS2表达与免疫细胞浸润的相关性,免疫调节剂,免疫周期,和肝癌免疫微环境中的免疫标志物。此外,qRT-PCR和Westernblot用于验证HCC患者组织中的基因表达。
开放数据库分析证实,CKS2在HCC中高表达,并且与HCC患者的不良预后有关。HCC中CKS2的两个甲基化位点的异常甲基化水平有助于其高表达,并与生存率显着相关。CKS2表达与大多数免疫调节剂和B和CD8T细胞的浸润水平呈正相关。树突状细胞,和巨噬细胞,特别是耗尽的CD8+T细胞。此外,在HCC中,CKS2的表达也与免疫周期步骤和多种免疫标志物显著相关.在mRNA和蛋白质水平的HCC中证实了高CKS2表达,显示与正常组织相比的显著增加。
CKS2是HCC的潜在预后生物标志物,可通过其对免疫环境的影响促进HCC的进展。此外,CKS2与免疫标志物之间呈正相关,突出了其作为免疫治疗靶点的潜力。
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