Loss of IL-34 Expression Indicates Poor Prognosis in Patients With Lung Adenocarcinoma

Zhendong Wang; Jun Zhu; Tianyi Wang; Hao Zhou; Jinjie Wang; Zhanghao Huang; Haijian Zhang; Jiahai Shi

doi:10.3389/fonc.2021.639724

Loss of IL-34 Expression Indicates Poor Prognosis in Patients With Lung Adenocarcinoma

Front Oncol. 2021 Jul 16:11:639724. doi: 10.3389/fonc.2021.639724. eCollection 2021.

Authors

Zhendong Wang^{1

2}, Jun Zhu^{1

2}, Tianyi Wang¹, Hao Zhou^{1

2}, Jinjie Wang^{1

2}, Zhanghao Huang^{1

2}, Haijian Zhang³, Jiahai Shi^{1

2}

Affiliations

¹ 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.
² Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
³ Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.

Abstract

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.

Keywords: The Cancer Genome Atlas; interleukin 34; lung adenocarcinoma; prognosis; tissue microarray.