生物信息学和实验方法将载脂蛋白 L2 鉴定为肺腺癌的诊断和预后指标。
Bioinformatics and experimental approach identify lipocalin 2 as a diagnostic and prognostic indicator for lung adenocarcinoma.
机构信息
Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Department of Pulmonary and Critical Care Medicine, Shaanxi Provincial Second People's Hospital, Xi'an 710005, China.
出版信息
Int J Biol Macromol. 2024 Jun;272(Pt 2):132797. doi: 10.1016/j.ijbiomac.2024.132797. Epub 2024 Jun 6.
BACKGROUND
lipocalin 2 (LCN2) is a secreted glycoprotein that plays key roles in tumorigenesis and progression. Interestingly, LCN2 appears to have a contradictory function in developing lung adenocarcinoma (LUAD). Thus, we intend to explore the role of LCN2 in LUAD through bioinformatics and experimental validation.
METHODS
LCN2 expression of LUAD was investigated in the TCGA, TIMER and HPA databases. The relationship between LCN2 and prognosis was investigated by KM plotter, TCGA and GEO databases. GO, KEGG and protein-protein interactions network analysis were conducted to investigate the potential mechanism of LCN2. The relevance of LCN2 to cancer-immune infiltrates was investigated in the TCGA and TIMER databases. Quantitative reverse transcription PCR, western blot and enzyme-linked immunosorbent assay were performed to identify the expression level of LCN2 in cells and serum samples. The CCK-8, wound healing and transwell assay were used to confirm the effect of LCN2 on cell proliferation, migration and invasion in LUAD. The receiver operating characteristic curve was utilized to assess the diagnostic efficiency of LCN2 further.
RESULTS
LCN2 expression was significantly upregulated in LUAD (P < 0.05), and was correlated with the clinical stage, tumor size, lymph node metastasis and distant metastasis (P < 0.05). There was a high correlation between high LCN2 and worse prognosis in LUAD. Functional network analysis suggested that LCN2 was associated with multiple signal pathways in cancers, such as JAK-STAT, TNF, NF-κB, HIF-1 and PI3K-Akt signal pathways. In addition, the knockdown of LCN2 significantly inhibited the ability of cell proliferation, migration and invasion. Immune infiltration analysis indicated that LCN2 is associated with multiple immune cell infiltration. Notably, LCN2 demonstrated high diagnostic efficiency for LUAD (AUC = 0.818, P < 0.05), especially for stage III-IV patients could reach 0.895.
CONCLUSIONS
LCN2 as an oncogenic glycoprotein promotes the cancer progression related to immune infiltrates, which might be a potential diagnostic and prognostic marker in LUAD.
背景
脂钙蛋白 2（LCN2）是一种分泌性糖蛋白，在肿瘤发生和进展中发挥关键作用。有趣的是，LCN2 在发展中的肺腺癌（LUAD）中似乎具有矛盾的功能。因此，我们打算通过生物信息学和实验验证来探索 LCN2 在 LUAD 中的作用。
方法
在 TCGA、TIMER 和 HPA 数据库中研究 LUAD 中的 LCN2 表达。通过 KM plotter、TCGA 和 GEO 数据库研究 LCN2 与预后的关系。进行 GO、KEGG 和蛋白质-蛋白质相互作用网络分析，以研究 LCN2 的潜在机制。在 TCGA 和 TIMER 数据库中研究 LCN2 与癌症免疫浸润的相关性。进行定量逆转录 PCR、western blot 和酶联免疫吸附测定，以鉴定细胞和血清样本中 LCN2 的表达水平。CCK-8、划痕愈合和 Transwell 测定用于确认 LCN2 对 LUAD 中细胞增殖、迁移和侵袭的影响。利用受试者工作特征曲线进一步评估 LCN2 的诊断效率。
结果
LCN2 在 LUAD 中表达明显上调（P<0.05），与临床分期、肿瘤大小、淋巴结转移和远处转移有关（P<0.05）。在 LUAD 中，高 LCN2 与预后不良高度相关。功能网络分析表明，LCN2 与癌症中的多个信号通路有关，如 JAK-STAT、TNF、NF-κB、HIF-1 和 PI3K-Akt 信号通路。此外，LCN2 的敲低显著抑制了细胞增殖、迁移和侵袭的能力。免疫浸润分析表明，LCN2 与多种免疫细胞浸润有关。值得注意的是，LCN2 对 LUAD 具有较高的诊断效率（AUC=0.818，P<0.05），尤其是对于 III 期和 IV 期患者可达 0.895。
结论
LCN2 作为一种致癌糖蛋白，促进与免疫浸润有关的癌症进展，这可能是 LUAD 中潜在的诊断和预后标志物。
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