miRNA sequencing reveals miRNA-4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica-related pulmonary fibrosis: A multistage study

Minjie Chu; Shuangshuang Wu; Wei Wang; Liping Mao; Yuhui Yu; Liying Jiang; Weiyan Yuan; Mingjiong Zhang; Lingli Sang; Qiqing Huang; Tian Tian; Lei Han; Xun Zhuang; Zuo-Feng Zhang; Jianqing Wu

doi:10.1111/resp.13714

miRNA sequencing reveals miRNA-4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica-related pulmonary fibrosis: A multistage study

Respirology. 2020 May;25(5):511-517. doi: 10.1111/resp.13714. Epub 2019 Oct 29.

Authors

Minjie Chu^{1

2}, Shuangshuang Wu³, Wei Wang⁴, Liping Mao⁵, Yuhui Yu¹, Liying Jiang⁶, Weiyan Yuan⁷, Mingjiong Zhang³, Lingli Sang¹, Qiqing Huang³, Tian Tian¹, Lei Han⁸, Xun Zhuang¹, Zuo-Feng Zhang², Jianqing Wu³

Affiliations

¹ Department of Epidemiology, School of Public Health, Nantong University, Nantong, China.
² Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA.
³ Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
⁴ Department of Occupational Health, Center for Disease Control and Prevention of Wuxi, Wuxi, China.
⁵ Department of Oncology, the Sixth People's Hospital of Nantong, Nantong, China.
⁶ Collaborative Research Center, Shanghai University of Medicine and Health Sciences, Shanghai, China.
⁷ Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong, China.
⁸ Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.

PMID: 31663225
DOI: 10.1111/resp.13714

Abstract

Background and objective: This study aimed to identify miRNA as potential diagnostic biomarkers for silica-related pulmonary fibrosis (SPF).

Methods: We first performed a comprehensive miRNA-seq screening in PBL of eight subjects exposed to silica dust (four individuals with SPF and four healthy controls). The promising miRNA were then evaluated in the first-stage validation using an independent GEO data set (GSE80555) of 6 subjects (3 individuals with SPF and 3 healthy controls), followed by a second-stage validation using 120 subjects exposed to silica dust (60 individuals with SPF and 60 healthy controls).

Results: Thirty-five miRNA showed strong expression differences in miRNA-seq screening, while miRNA-4508 (P = 9.52 × 10^-3 ) was retained as a candidate after the first-stage validation (GSE80555), which was further confirmed in the second-stage validation with similar and strong effect (P = 9.93 × 10^-17 ). ROC analysis showed that miRNA-4508 could distinguish SPF cases from healthy controls with high AUC (0.886), with sensitivity of 81.7% and specificity of 86.7%. In addition, the miRNA-4508 upstream rs6576457 mutant A allele exhibited a strong association with susceptibility to SPF (OR = 1.64, 95% CI = 1.20-2.23, P = 0.002), while eQTL analysis revealed a potential association between different genotypes of rs6576457 and miRNA-4508 expression (P = 0.068) in 60 healthy subjects with silica dust exposure.

Conclusion: miRNA-4508 may be a potential diagnostic marker for SPF, and rs6576457, a functional variant of miRNA-4508, may affect SPF susceptibility. The detailed mechanism of action of this miRNA remains to be elucidated.

Keywords: microRNA sequencing; microRNA-4508; rs6576457; silica-related pulmonary fibrosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Case-Control Studies
Female
Genetic Markers / immunology
Genetic Predisposition to Disease
Humans
Lymphocytes / immunology
Male
MicroRNAs* / genetics
MicroRNAs* / immunology
Pulmonary Fibrosis* / diagnosis
Pulmonary Fibrosis* / etiology
Pulmonary Fibrosis* / genetics
Pulmonary Fibrosis* / immunology
ROC Curve
Reproducibility of Results
Silicon Dioxide / immunology*

Substances

Genetic Markers
MicroRNAs
Silicon Dioxide