非小细胞肺癌（NSCLC）包括肺鳞状细胞癌（LUSC）和肺腺癌（LUAD）亚型，是一种五年生存率较差的恶性肿瘤。迫切需要鉴定新的强大的NSCLC诊断生物标志物、预后生物标志物和潜在的治疗靶点。利用UCSC Xena、UALCAN和GEO数据库筛选和分析NSCLC的差异表达基因、调控模式和遗传/表观遗传改变。使用UCSC Xena数据库、GEO数据库、组织微阵列和免疫组织化学染色分析来评估诊断和预后价值。进行功能获得测定来检查这些作用。使用ESTIMATE、TIMER、Linked Omics、STRING和DAVID算法分析潜在的分子机制。NR3C2被确定为NSCLC中潜在的重要分子。 NR3C2在NSCLC、LUAD、LUSC组织中低表达，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表明，NR3C2 表达模式的改变对 NSCLC、LUAD，尤其是 LUSC 患者具有诊断价值。 NR3C2 表达水平降低可以帮助预测 NSCLC 和 LUAD 患者的不良预后，但不能帮助预测 LUSC 患者的不良预后。这些结果已通过数据库分析和组织微阵列上的真实临床样本得到证实。拷贝数变异导致 NSCLC 和 LUAD 中 NR3C2 表达水平较低，而启动子 DNA 甲基化参与 LUSC 中 NR3C2 的下调。 NR3C2启动子的两个甲基化位点对LUSC诊断具有较高的敏感性和特异性，具有临床应用潜力。 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 共表达基因参与许多癌症相关信号通路，进一步支持 NR3C2 在 NSCLC 中的潜在重要作用。NR3C2 是 NSCLC 中一种新型的潜在诊断和预后生物标志物和治疗靶点。© 2024 作者。约翰·威利 (John Wiley) 出版的《癌症创新》

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.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.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.NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.© 2024 The Authors. Cancer Innovation published by John Wiley & Sons Ltd on behalf of Tsinghua University Press.