Wang Zhendong, Zhu Jun, Wang Tianyi, Zhou Hao, Wang Jinjie, Huang Zhanghao, Zhang Haijian, Shi Jiahai
Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases, and Research Institution of Translational Medicine in Cardiothoracic Diseases, Affiliated Hospital of Nantong University, Nantong, China.
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
Front Oncol. 2021 Jul 16;11:639724. doi: 10.3389/fonc.2021.639724. eCollection 2021.
Interleukin 34 (IL-34), an additional ligand of the colony-stimulating factor-1 receptor (CSF-1R), promotes the secretion of pro-inflammatory cytokines and stimulates NF-κB and JNK-related signaling pathways. However, the potential mechanism and prognostic value of IL-34 in lung adenocarcinoma (LUAD) remain obscure. In this study, IL-34 was found to be downregulated in LUAD tissues compared with para-carcinoma tissues, and loss of IL-34 expression was correlated with shorter overall survival (OS), which was validated by bioinformatics\ analysis in TCGA (The Cancer Genome Atlas) cohort and immunohistochemical analysis in the NTU (Nantong University) cohort, respectively. Subsequently, loss of IL-34 promotes negative regulation of the immune system and inhibits the infiltration of immune cells. Moreover, IL-34 deficiency was shown to be an independent adverse prognostic factor for patients with LUAD, and subgroup analysis indicated that IL-34 might contribute to the stratified management of patients with LUAD. IL-34-based nomogram model significantly improved the accuracy of prognostic predictions for OS of patients with LUAD, both in the TCGA cohort and the NTU cohort. Taken together, our data suggested that loss of IL-34 expression is associated with poor prognosis and negative regulation of the immune system of patients with LUAD, contributing to the stratified management of patients with LUAD.
白细胞介素34(IL-34)是集落刺激因子-1受体(CSF-1R)的另一种配体,可促进促炎细胞因子的分泌,并刺激NF-κB和JNK相关信号通路。然而,IL-34在肺腺癌(LUAD)中的潜在机制和预后价值仍不清楚。在本研究中,发现与癌旁组织相比,LUAD组织中IL-34表达下调,IL-34表达缺失与较短的总生存期(OS)相关,这分别在TCGA(癌症基因组图谱)队列中的生物信息学分析和NTU(南通大学)队列中的免疫组织化学分析中得到验证。随后,IL-34的缺失促进免疫系统的负调节并抑制免疫细胞的浸润。此外,IL-34缺乏被证明是LUAD患者的独立不良预后因素,亚组分析表明IL-34可能有助于LUAD患者的分层管理。基于IL-34的列线图模型显著提高了TCGA队列和NTU队列中LUAD患者OS预后预测的准确性。综上所述,我们的数据表明,IL-34表达缺失与LUAD患者的不良预后和免疫系统负调节相关,有助于LUAD患者的分层管理。