Table_3_NUF2 Expression Promotes Lung Adenocarcinoma Progression and Is Associated With Poor Prognosis.xlsx

Aberrant expression of the gene encoding the Ndc80 kinetochore complex component (NUF2) reportedly contributes to the progression of several human cancers. However, the functional roles of NUF2 and their underlying mechanisms in lung adenocarcinoma (LUAD) are largely unknown. The current study aimed to investigate the role of NUF2 in LUAD tumorigenesis. Here, TCGA, ONCOMINE, the Human Protein Atlas, UALCAN, and the results of our cohort were used to analyze the expression of NUF2 in LUAD. A Kaplan–Meier analysis and univariate and multivariate Cox regression analyses were performed to estimate the prognostic values of NUF2 expression in the Cancer Genome Atlas cohort. We studied the effects of NUF2 expression on proliferation, migration, invasion, and tumor growth using LUAD cell lines. Gene set enrichment analysis (GSEA) was used to analyze the pathways and biological function enrichment of NUF2 in LUAD. The ssGSEA database was used to analyze the relationship between NUF2 expression and immune cell infiltration in LUAD. Results revealed elevated expression of NUF2 in LUAD specimens. Patients overexpressing NUF2 had poor prognoses relative to those with low NUF2 expression. Knockdown of NUF2 suppressed the proliferation, migration, invasion, epithelial-mesenchymal transition, and colony formation of LUAD cells. Moreover, NUF2 knockdown induced cell cycle arrest at the G0/G1 phase. Gene Ontology and GSEA analyses suggested that NUF2 may be involved in immunity, proliferation, and apoptosis-related pathways. NUF2 overexpression was positively correlated with differential immune cell infiltration. In conclusion, NUF2 expression was associated with the clinical phenotype of LUAD and hence has potential implications in LUAD treatment.

编码Ndc80动粒复合物组分的基因（NUF2）的异常表达，据报道可促进多种人类癌症的进展。然而，NUF2在肺腺癌（LUAD）中的功能作用及其潜在分子机制，目前尚未完全阐明。本研究旨在探讨NUF2在肺腺癌发生发展中的作用。本研究借助TCGA、ONCOMINE、人类蛋白图谱（Human Protein Atlas）、UALCAN数据库以及本课题组自建队列的实验结果，分析了NUF2在肺腺癌组织中的表达水平。通过Kaplan-Meier生存分析、单因素与多因素Cox回归分析，对癌症基因组图谱（The Cancer Genome Atlas, TCGA）队列中NUF2表达的预后价值进行了评估。本研究利用肺腺癌细胞系，探究了NUF2表达对细胞增殖、迁移、侵袭以及肿瘤生长的影响。采用基因集富集分析（Gene Set Enrichment Analysis, GSEA）分析了NUF2在肺腺癌中的通路富集与生物学功能富集特征。借助单样本基因集富集分析（single-sample Gene Set Enrichment Analysis, ssGSEA）数据库，分析了NUF2表达与肺腺癌中免疫细胞浸润的相关性。研究结果显示，肺腺癌组织标本中NUF2的表达水平显著升高。与NUF2低表达患者相比，NUF2高表达患者的预后较差。敲低NUF2可抑制肺腺癌细胞的增殖、迁移、侵袭、上皮间质转化（epithelial-mesenchymal transition, EMT）以及集落形成能力。此外，敲低NUF2可诱导肺腺癌细胞发生G0/G1期细胞周期阻滞。基因本体（Gene Ontology, GO）分析与基因集富集分析结果显示，NUF2可能参与免疫、增殖以及凋亡相关的信号通路。NUF2高表达与免疫细胞浸润差异呈正相关。综上，NUF2的表达与肺腺癌的临床表型密切相关，因此其在肺腺癌的临床治疗中具有潜在的应用价值。