关键词: NR3C2 diagnosis and prognosis expression regulation function immune cell infiltration non‐small cell lung cancer therapeutic target tumor microenvironment

来  源:   DOI:10.1002/cai2.122   PDF(Pubmed)

Abstract:
UNASSIGNED: Non-small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor 5-year survival rate. The identification of new powerful diagnostic biomarkers, prognostic biomarkers, and potential therapeutic targets in NSCLC is urgently required.
UNASSIGNED: The UCSC Xena, UALCAN, and GEO databases were used to screen and analyze differentially expressed genes, regulatory modes, and genetic/epigenetic alterations in NSCLC. The UCSC Xena database, GEO database, tissue microarray, and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values. Gain-of-function assays were performed to examine the roles. The ESTIMATE, TIMER, Linked Omics, STRING, and DAVID algorithms were used to analyze potential molecular mechanisms.
UNASSIGNED: NR3C2 was identified as a potentially important molecule in NSCLC. NR3C2 is expressed at low levels in NSCLC, LUAD, and LUSC tissues, which is significantly related to the clinical indexes of these patients. Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC, LUAD, and especially LUSC patients. Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients. These results have been confirmed both with database analysis and real-world clinical samples on a tissue microarray. Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD, while promoter DNA methylation is involved in its downregulation in LUSC. Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential. NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration. NR3C2 co-expressed genes are involved in many cancer-related signaling pathways, further supporting a potentially significant role of NR3C2 in NSCLC.
UNASSIGNED: NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.
摘要:
非小细胞肺癌(NSCLC),包括肺鳞状细胞癌(LUSC)和肺腺癌(LUAD)亚型,是一种恶性肿瘤类型,5年生存率低。识别新的强大的诊断生物标志物,预后生物标志物,和NSCLC的潜在治疗靶点是迫切需要的。
UCSCXena,UALCAN,和GEO数据库用于筛选和分析差异表达基因,监管模式,非小细胞肺癌的遗传/表观遗传改变。UCSCXena数据库,GEO数据库,组织微阵列,和免疫组织化学染色分析用于评估诊断和预后价值。进行功能增益测定以检查作用。估计,TIMER,链接的组学,STRING,和DAVID算法用于分析潜在的分子机制。
NR3C2被鉴定为NSCLC中潜在的重要分子。NR3C2在NSCLC中低水平表达,LUAD,和LUSC组织,这与这些患者的临床指标显着相关。受试者工作特征曲线分析提示NR3C2表达模式改变对NSCLC有诊断价值,LUAD,尤其是LUSC患者。NR3C2表达水平的降低可以帮助预测NSCLC和LUAD患者的不良预后,而不是LUSC患者。这些结果已通过数据库分析和组织微阵列上的真实世界临床样品得到证实。拷贝数变异有助于NSCLC和LUAD中NR3C2的低表达水平,而启动子DNA甲基化参与其在LUSC中的下调。两个NR3C2启动子甲基化位点对LUSC诊断具有较高的敏理性和特异性,具有临床运用潜力。NR3C2可能是NSCLC发生发展的关键参与者,与肿瘤微环境和免疫细胞浸润密切相关。NR3C2共表达的基因参与许多癌症相关的信号通路,进一步支持NR3C2在NSCLC中的潜在重要作用。
NR3C2是一种新的NSCLC潜在的诊断和预后生物标志物和治疗靶点。
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