非小细胞肺癌中胰岛素样生长因子结合蛋白1表达及中性粒细胞铁死亡导致肿瘤免疫抑制的临床特征
Clinical Characterization of the Expression of Insulin-Like Growth Factor Binding Protein 1 and Tumor Immunosuppression Caused by Ferroptosis of Neutrophils in Non-Small Cell Lung Cancer.
作者信息
Wang Yuandi, Xing Lijuan, Deng Lexiu, Wang Xinsheng, Xu Dandan, Wang Bu, Zhang Zhihua
机构信息
Graduate School, Hebei North University, Zhangjiakou City, Hebei Province, People's Republic of China.
Department of Respiratory and Critical Care Clinical Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou City, Hebei Province, People's Republic of China.
出版信息
Int J Gen Med. 2023 Mar 21;16:997-1015. doi: 10.2147/IJGM.S401225. eCollection 2023.
PURPOSE
The efficacy of immunotherapy for non-small cell lung cancer (NSCLC) is limited owing to cold tumors and drug resistance. Therefore, it is important to identify the molecular mechanisms underlying immune evasion in NSCLC. Spontaneous ferroptosis of neutrophils has been suggested as a key mechanism of immunosuppression in cancer. Insulin-like growth factor binding protein 1 (IGFBP1) plays an important role in immune infiltration in several cancers. However, the role of IGFBP1 in NSCLC is unknown. Therefore, in this study, we aimed to investigate the association of mRNA expression with infiltration of myeloid-derived suppressor cells and prognosis in NSCLC.
PATIENTS AND METHODS
Retrospective RNA-seq data from 990 patients in the Cancer Genome Atlas (TCGA) database were analyzed in relation to patient clinical characteristics. The Timer2 database was used to assess immune infiltration, and the FerrDb V2 database was used to obtain ferroptosis-related genes. Finally, the results were validated by the proteomic analysis of serum samples collected from six patients with NSCLC and six healthy individuals.
RESULTS
expression was enriched in lung adenocarcinoma samples and positively correlated with the pathological grade of NSCLC. expression was an independent prognostic factor for the overall survival of patients with NSCLC. In addition, expression correlated with myeloid-derived suppressor cell infiltration. Notably, Gene Ontology analysis of -related genes revealed that the major molecular functions of their protein products were related to NADP 1-oxidoreductase activity. Furthermore, expression levels of multiple ferroptosis suppressor genes positively correlated with expression.
CONCLUSION
High expression indicates a poor prognosis in patients with NSCLC, which may be related to tumor immunosuppression caused by neutrophil ferroptosis.
目的
由于“冷肿瘤”和耐药性，免疫疗法对非小细胞肺癌（NSCLC）的疗效有限。因此，确定NSCLC免疫逃逸的分子机制很重要。中性粒细胞的自发性铁死亡被认为是癌症免疫抑制的关键机制。胰岛素样生长因子结合蛋白1（IGFBP1）在几种癌症的免疫浸润中起重要作用。然而，IGFBP1在NSCLC中的作用尚不清楚。因此，在本研究中，我们旨在探讨mRNA表达与NSCLC中髓源性抑制细胞浸润及预后的关系。
患者和方法
分析癌症基因组图谱（TCGA）数据库中990例患者的回顾性RNA测序数据，并与患者临床特征相关联。使用Timer2数据库评估免疫浸润，使用FerrDb V2数据库获取铁死亡相关基因。最后，通过对6例NSCLC患者和6例健康个体采集的血清样本进行蛋白质组学分析来验证结果。
结果
在肺腺癌样本中表达丰富，且与NSCLC的病理分级呈正相关。表达是NSCLC患者总生存的独立预后因素。此外，表达与髓源性抑制细胞浸润相关。值得注意的是，对相关基因的基因本体分析表明，其蛋白质产物的主要分子功能与NADP 1-氧化还原酶活性有关。此外，多个铁死亡抑制基因的表达水平与表达呈正相关。
结论
高表达表明NSCLC患者预后不良，这可能与中性粒细胞铁死亡引起的肿瘤免疫抑制有关。
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