The miR-582/CD1B Axis Is Involved in Regulation of Dendritic Cells and Is Associated with Clinical Outcomes in Advanced Lung Adenocarcinoma.

Jun Guo,Yi Jin,Hui Jin,Yanfeng Xi,Da Jiang,Jian Guo

doi:10.1155/2020/4360930

Abstract

The involvement of immune dysfunction in the pathogenesis of lung cancer has been extensively studied. However, the potential molecular mechanisms through which the tumor immune response affects drug resistance are still unclear. Accordingly, in this study, we evaluated deviations in the immune cell landscape among patients with different stages of lung adenocarcinoma to identify key microRNAs and their targets associated with patient outcomes. CIBERSORT was used for estimating the proportions of immune cells in various lung tissues. Significantly different adaptive and innate immune cell types, including memory B cells, CD8+ T cells, resting dendritic cells, and resting mast cells, were selected. Comparative studies and survival analyses were carried out. We found that potential genes and microRNAs involved in immune responses were associated with patient outcomes. Specifically, miR-582/CD1B, which are involved in resting and activated dendritic cells, may be potential novel biomarkers for immunotherapy. An independent dataset of miRNA microarray profiles was used to validate the expression of mature miR-582-5p in patients with advanced lung adenocarcinoma. Alternative treatments, including immunotherapies and chemotherapy, are urgently needed to improve outcomes in patients with lung cancer. Thus, our findings could provide insights into the selection of novel microRNAs targeting immune genes and could improve the efficacy of immunotherapy by disrupting tumor function and promoting immune infiltration in patients with advanced lung adenocarcinoma.

Highlights

Lung adenocarcinoma (LADC) is a major cause of cancerrelated death worldwide, accounting for approximately 40% of non-small-cell lung cancers (NSCLCs) [1, 2]
Gene expression profiles from 495 LADC samples were downloaded from the UCSC Xena platform [24]
The efficacy of treatments for lung cancer is limited by a lack of early detection methods and the acquisition of drug resistance

Summary

Introduction

Lung adenocarcinoma (LADC) is a major cause of cancerrelated death worldwide, accounting for approximately 40% of non-small-cell lung cancers (NSCLCs) [1, 2]. Patients with nonmetastatic lung cancer typically undergo surgical resection. Patients with metastatic or advanced stage disease are treated with chemotherapy alone or in combination with radiation [3]. Many innovative therapies, including immunotherapies and molecular targeted therapies, have been developed, the survival rate of patients with LADC is still low because of histological subtype tumor heterogeneity, poor understanding of disease pathogenesis, and drug resistance. Additional molecular characterization of the LADC landscape could help researchers and clinicians to identify novel biomarkers or molecular targets, design novel therapeutic strategies, and improve patient outcomes [4]. The import roles of the tumor microenvironment (TME) in the initiation and progression of primary and secondary lung carcinoma have been uncovered, and the TME has been recognized as a target-rich environment for novel anticancer agents [5,6,7]. Several approved drugs targeting different biomarkers in the TME have been

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