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二硫化物下垂相关基因NCKAP1的泛癌分析及其对肺腺癌的预后价值。

Pan-cancer Analysis of the Disulfidptosis-related Gene NCKAP1 and Its Prognostic Value for Lung Adenocarcinoma.

发表日期:2023
作者: Ankang Zhu, Yan Zong, Shuai Wei, Yinuo Li, Yan Fan, Shaodong Liu, Xingcai Gao
来源: Cell Death & Disease

摘要:

二硫键相关基因的 nck 相关蛋白 1 (NCKAP1) 在程序性细胞死亡中至关重要。然而,缺乏对NCKAP1在泛癌中的生物学意义的全面分析。癌症的基因表达矩阵和临床表达信息来自癌症基因组图谱(TCGA)和基因型组织表达(GTEX)数据库。利用Timer2.0、HPA、GEPIA、STRING、cBioPortal、UALCAN和CellMiner数据库对泛癌中NCKAP1表达、生物学功能、基因突变、免疫细胞浸润、DNA甲基化和药物敏感性谱进行综合分析。基于COX回归分析和Kaplan-Meier(K-M)曲线研究NCKAP1的预后价值。建立列线图验证 NCKAP1 对 LUAD 的临床价值。通过单样本基因集富集分析(ssGSEA)研究NCKAP1与免疫细胞及信号通路的相关性。使用 PCR、Western Blot (WB) 和 Transwell 检测进行验证。肿瘤和正常样本之间 NCKAP1 的表达水平、突变水平和甲基化水平存在显着差异。 NCKAP1影响多种癌症的预后。 NCKAP1 与微卫星不稳定性 (MSI) 和肿瘤突变负荷 (TMB) 密切相关。基因本体论(GO)和京都基因和基因组百科全书(KEGG)分析表明NCKAP1与细胞死亡和肿瘤免疫密切相关。 NCKAP1的表达影响对多种药物的敏感性。此外,NCKAP1 是 LUAD 患者预后的独立预测因子。 ssGSEA结果显示NCKAP1表达升高与多种免疫相关信号通路呈正相关。 PCR分析显示LUAD细胞中NCKAP1的表达增加。 Transwell侵袭实验显示NCKAP1过表达导致LUAD细胞侵袭增强。我们全面分析了NCKAP1与泛癌的关系及其潜在的临床价值。 NCKAP1可能是多种癌症(尤其是LUAD)的潜在免疫标志物,为癌症治疗提供新的见解和见解。©作者。
The nck-associated protein 1 (NCKAP1) of the disulfidptosis-related gene is essential in programmed cell death. However, a comprehensive analysis of the biological significance of NCKAP1 in pan-cancer is lacking.Gene expression matrices and clinical expression information of cancers were obtained from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEX) databases. A comprehensive analysis of NCKAP1 expression, biological function, gene mutation, immune cell infiltration, DNA methylation, and drug sensitivity profiles in pan-cancer was performed using the Timer2.0, HPA, GEPIA, STRING, cBioPortal, UALCAN and CellMiner databases. The prognostic value of NCKAP1 was investigated based on COX regression analysis and the Kaplan-Meier(K-M) curves. A nomogram was established to verify the clinical value of NCKAP1 for LUAD. The correlation between NCKAP1 and immune cells and signaling pathways were investigated by single-sample gene set enrichment analysis(ssGSEA). Validation was performed using PCR, Western Blot (WB), and Transwell assays.Significant differences in expression levels, mutation levels, and methylation levels of NCKAP1 between tumor and normal samples. NCKAP1 affects the prognosis of various cancers. NCKAP1 is strongly associated with microsatellite instability (MSI) and tumor mutational burden (TMB). The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicate that NCKAP1 is strongly associated with cell death and tumor immunity. The expression of NCKAP1 affects the sensitivity to various drugs. Moreover, NCKAP1 is an independent predictor of prognosis in LUAD patients. The results of ssGSEA showed that elevated NCKAP1 expression was positively correlated with multiple immune-related signaling pathways. PCR analysis showed that the expression of NCKAP1 was increased in LUAD cells. Transwell invasion assay showed that overexpression of NCKAP1 resulted in enhanced invasion of LUAD cells.We comprehensively analyzed the relationship between NCKAP1 and pan-cancer and its potential clinical value. NCKAP1 could be a potential immune marker for various cancers (especially LUAD), providing new insights and insights for cancer therapy.© The author(s).