肺腺癌中 GNPNAT1 的独立预后潜力。
Independent Prognostic Potential of GNPNAT1 in Lung Adenocarcinoma.
机构信息
Department of Laboratory Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China.
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and The Berlin Institute of Health, Berlin, Germany.
出版信息
Biomed Res Int. 2020 Oct 29;2020:8851437. doi: 10.1155/2020/8851437. eCollection 2020.
BACKGROUND
Glucosamine-Phosphate N-Acetyltransferase 1 (GNPNAT1) is a critical enzyme in the biosynthesis of uridine diphosphate-N-acetylglucosamine. It has many important functions, such as protein binding, monosaccharide binding, and embryonic development and growth. However, the role of GNPNAT1 in lung adenocarcinoma (LUAD) remains unclear.
METHODS
In this study, we explored the expression pattern and prognostic value of GNPNAT1 in LUAD across TCGA and GEO databases and assessed its independent prognostic value via Cox analysis. LinkedOmics and GEPIA2 were applied to investigate coexpression and functional networks associated with GNPNAT1. The TIMER web tool was deployed to assess the correlation between GNPNAT1 and the main six types of tumor-infiltrating immune cells. Besides, the correlations between GNPNAT1 and the LUAD common genetic mutations, TMB, and immune signatures were examined.
RESULTS
GNPNAT1 was validated upregulated in tumor tissues in TCGA-LUAD and GEO cohorts. Moreover, in both TCGA and GEO cohorts, high GNPNAT1 expression was found to be associated with poor overall survival. Cox analysis showed that high GNPNAT1 expression was an independent risk factor for LUAD. Functional network analysis suggested that GNPNAT1 regulates cell cycle, ribosome, proteasome, RNA transport, and spliceosome signaling through pathways involving multiple cancer-related kinases and E2F family. In addition, GNPNAT1 correlated with infiltrating levels of B cells, CD4+ T cells, and dendritic cells. B cells and dendritic cells could predict the outcome of LUAD, and B cells and CD4+ T cells were significant independent risk factors. The TMB and mutations of KRAS, EGFR, STK11, and TP53 were correlated with GNPNAT1. At last, the correlation analysis showed GNPNAT1 correlated with most of the immune signatures we performed.
CONCLUSION
Our findings showed that GNPNAT1 was correlated to the prognosis and immune infiltration of LUAD. In particular, the tight relationship between GNPNAT1 and B cell marker genes may be the epicenter of the immune response and one of the key factors affecting the prognosis. Our findings laid the foundation for further research on the immunomodulatory role of GNPNAT1 in LUAD.
背景
磷酸葡萄糖胺-N-乙酰转移酶 1（GNPNAT1）是尿苷二磷酸-N-乙酰葡萄糖胺生物合成中的关键酶。它具有许多重要功能，如蛋白质结合、单糖结合以及胚胎发育和生长等。然而，GNPNAT1 在肺腺癌（LUAD）中的作用尚不清楚。
方法
本研究通过 TCGA 和 GEO 数据库探讨 GNPNAT1 在 LUAD 中的表达模式和预后价值，并通过 Cox 分析评估其独立预后价值。应用 LinkedOmics 和 GEPIA2 分析与 GNPNAT1 相关的共表达和功能网络。利用 TIMER 网络工具评估 GNPNAT1 与六种主要肿瘤浸润免疫细胞之间的相关性。此外，还研究了 GNPNAT1 与 LUAD 常见遗传突变、TMB 和免疫特征之间的相关性。
结果
在 TCGA-LUAD 和 GEO 队列中验证了 GNPNAT1 在肿瘤组织中上调。此外，在 TCGA 和 GEO 队列中，高 GNPNAT1 表达与总生存期不良相关。Cox 分析显示，高 GNPNAT1 表达是 LUAD 的独立危险因素。功能网络分析表明，GNPNAT1 通过涉及多种癌症相关激酶和 E2F 家族的途径，调节细胞周期、核糖体、蛋白酶体、RNA 转运和剪接体信号。此外，GNPNAT1 与 B 细胞、CD4+T 细胞和树突状细胞的浸润水平相关。B 细胞和树突状细胞可预测 LUAD 的预后，B 细胞和 CD4+T 细胞是显著的独立危险因素。TMB 和 KRAS、EGFR、STK11 和 TP53 的突变与 GNPNAT1 相关。最后，相关性分析表明 GNPNAT1 与我们进行的大多数免疫特征相关。
结论
本研究结果表明，GNPNAT1 与 LUAD 的预后和免疫浸润相关。特别是，GNPNAT1 与 B 细胞标志物基因之间的紧密关系可能是免疫反应的核心，也是影响预后的关键因素之一。我们的研究结果为进一步研究 GNPNAT1 在 LUAD 中的免疫调节作用奠定了基础。
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