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

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.

• Authors: 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
• Journal: Respirology (Carlton, Vic.) (Respirology) Vol. 25 Issue 5 Pg. 511-517 (05 2020) ISSN: 1440-1843 [Electronic] Australia
• PMID: 31663225 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Asian Pacific Society of Respirology.

Chemical References

• Genetic Markers
• MicroRNAs
• Silicon Dioxide

Topics

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