GPI Is a Prognostic Biomarker and Correlates With Immune Infiltrates in Lung Adenocarcinoma.

GPI Is a Prognostic Biomarker and Correlates With Immune Infiltrates in Lung Adenocarcinoma.
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GPI 是一种预后生物标志物,与肺腺癌的免疫浸润相关

DOI:
10.3389/fonc.2021.752642
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发表时间:
2021
影响因子:
4.7
通讯作者:
Luo Z
Luo Z
中科院分区:
医学3区
文献类型:
--
作者:
Han J;Deng X;Sun R;Luo M;Liang M;Gu B;Zhang T;Peng Z;Lu Y;Tian C;Yan Y;Luo Z

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葡萄糖-6-磷酸异构酶(GPI)在糖酵解和糖异生中起重要作用。然而,GPI在肺腺癌(LUAD)中的作用尚不清楚。方法从Cancer Genome Atlas (TCGA)和Gene Expression Omnibus (GEO)数据库中下载所有原始数据,并通过r3.2.2进行整合。利用TCGA、GEO和Oncomine数据库研究GPI的表达。免疫组织化学染色法检测临床标本中GPI的表达。通过TIMER和TISIDB数据库分析GPI与肿瘤免疫特性的相关性。使用GPI特异性sirna验证GPI表达对细胞增殖和细胞周期分布的作用。结果一般情况下,GPI以过表达为主,对LUAD的诊断和预后评估具有参考价值。GPI的上调与LUAD患者较差的总生存期、临床分期、N期和主要治疗结果相关。在机制上,我们确定了一个枢纽基因,其中包括56个gpi相关基因,这些基因与LUAD患者的细胞周期途径密切相关。敲低GPI诱导细胞增殖抑制和细胞周期阻滞。GPI表达与Th2细胞和调节性T细胞(Tregs)浸润水平呈正相关;相反,GPI的表达与CD8+ T细胞、中枢记忆T细胞、树突状细胞、巨噬细胞、肥大细胞和嗜酸性粒细胞的浸润水平呈负相关。GPI与LUAD中CD40L、IL6R、TMEM173等免疫刺激因子的表达呈负相关。结论GPI可能在细胞周期中发挥重要作用,可作为判断LUAD患者预后和免疫浸润的预后生物标志物。
Background Glucose-6-phosphate isomerase (GPI) plays an important role in glycolysis and gluconeogenesis. However, the role of GPI in lung adenocarcinoma (LUAD) remains unclear. Methods All original data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and integrated via R 3.2.2. GPI expression was explored with TCGA, GEO, and Oncomine databases. Immunohistochemistry staining was used to analyze GPI expression in clinical specimens. The correlations between GPI and cancer immune characteristics were analyzed via the TIMER and TISIDB databases. GPI-specific siRNAs were used to verify the role of GPI expression on cell proliferation and cell cycle distribution. Results In general, GPI is predominantly overexpressed and has reference value in the diagnosis and prognostic estimation of LUAD. Upregulated GPI was associated with poorer overall survival, clinical stage, N stage, and primary therapy outcome in LUAD. Mechanistically, we identified a hub gene that included a total of 56 GPI-related genes, which were tightly associated with the cell cycle pathway in LUAD patients. Knockdown of GPI induced cell proliferation inhibition and cell cycle arrest. GPI expression was positively correlated with infiltrating levels of Th2 cells and regulatory T cells (Tregs); in contrast, GPI expression was negatively correlated with infiltrating levels of CD8+ T cells, central memory T cells, dendritic cells, macrophages, mast cells, and eosinophils. GPI was negatively correlated with the expression of immunostimulators, such as CD40L, IL6R, and TMEM173, in LUAD. Conclusion GPI may play an important role in the cell cycle and can be used as a prognostic biomarker for determining the prognosis and immune infiltration in LUAD.
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