背景:NIFK作为Ki67的结合蛋白,在细胞的有丝分裂中起重要作用,与特定类型肿瘤的进展密切相关。然而,目前尚缺乏对NIFK在泛癌症中的系统分析,也没有足够的研究来探讨其在人类肿瘤中的作用。
方法:我们使用来自癌症基因组图谱(TCGA)的数据,通过大规模生物信息学分析,系统地评估了NIFK在人类癌症中的泛癌表达和突变。此外,我们探索了NIFK的泛癌症免疫学特征,尤其是结直肠腺癌(COAD)。此外,我们使用单细胞测序分析了NIFK在COAD组织不同细胞中的表达,并进行了GO,KEGG,和COAD中NIFK的基因集富集分析。最后,我们在体外实验中评估了NIFK敲低对大肠癌细胞系的影响。
结果:我们发现NIFK在几乎所有类型的肿瘤中都过表达,并显示出显着的预后功效。此外,NIFK与特定免疫特征之间的相关性,如免疫细胞浸润,免疫检查点基因,TMB,和MSI,提示NIFK可用于指导免疫治疗。随后,通过单细胞测序分析发现,肿瘤细胞中NIFK的表达显著上调,NIFK基因与肿瘤进展和免疫治疗反应密切相关。最后,我们进一步阐明了NIFK在结直肠癌中的作用,并发现NIFK表达下调可以抑制结直肠癌的增殖,迁移,结直肠癌细胞的侵袭能力。
结论:这项研究的结果表明,NIFK,作为泛癌基因的一员,将作为一系列癌症类型的生物标志物和潜在治疗靶点,为精准医学提供新的见解。
BACKGROUND: As a binding protein of Ki67, NIFK plays an important role in the mitosis of cells and is closely related to the progression of specific types of tumors. However, there is still a lack of systematic analysis of NIFK in pan-cancer and insufficient research to explore its role in human tumors.
METHODS: We systematically evaluated the pan-cancer expression and mutation of NIFK in human cancers using data from The Cancer Genome Atlas (TCGA) through large-scale bioinformatics analysis. In addition, we explored the pan-cancer immunological characteristics of NIFK, especially in colorectal adenocarcinoma (COAD). Furthermore, we used single-cell sequencing to analyze the expression of NIFK in different cells of COAD tissues and performed GO, KEGG, and gene set enrichment analysis of NIFK in COAD. Lastly, we evaluated the effects of NIFK knockdown on the colorectal cancer cell lines in in vitro experiment.
RESULTS: We found that NIFK was overexpressed in almost all types of tumors and showed significant prognostic efficacy. Additionally, correlations between NIFK and specific immune features, such as immune cell infiltration, immune checkpoint genes, TMB, and MSI, suggest that NIFK may be used to guide immunotherapy. Subsequently, it was found that the expression of NIFK was significantly upregulated in tumor cells through single-cell sequencing analysis, and the NIFK gene was closely associated with tumor progression and immune therapy response. Finally, we further elucidated the role of NIFK in colorectal cancer and found that downregulation of NIFK expression could inhibit the proliferation, migration, and invasion ability of colorectal cancer cells.
CONCLUSIONS: The results of this study demonstrated that NIFK, as a member of the pan-cancer genes, will serve as a biomarker and a potential therapeutic target for a range of cancer types, providing new insight into precision medicine.