MiRNA‐4508 a potential diagnostic biomarker for silica‐related pulmonary fibrosis

MicroRNA-4508 shows promise as a diagnostic marker for silica-related pulmonary fibrosis (SPF), while its functional variant rs6576457 has been shown to influence susceptibility to SPF, according to a study.

A comprehensive miRNA sequencing screening was carried out in peripheral blood leukocytes of eight individuals exposed to silica dust (four with SPF and four healthy controls). Then, the investigators examined the promising miRNA in the first-stage validation using an independent GEO data set (GSE80555) of six participants (three with SPF and three healthy controls). This was followed by a second-stage validation in 120 individuals exposed to silica dust (60 with SPF and 60 healthy controls).

Thirty-five miRNA demonstrated robust expression differences in miRNA-seq screening. After the first-stage validation (GSE80555), miRNA-4508 (p=9.52 x 10^-3) was retained as a candidate. The second-stage validation confirmed this, showing similar and strong effect (p=9.93 x 10^-17). In receiver operating characteristic (ROC) analysis, miRNA-4508 distinguished SPF cases from healthy controls with high area under the ROC curve (0.886; sensitivity, 81.7 percent; specificity, 86.7 percent).

Furthermore, a robust association was observed between the miRNA-4508 upstream rs6576457 mutant A allele and susceptibility to SPF (odds ratio, 1.64, 95 percent confidence interval, 1.20–3.32; p=0.002). In expression quantitative trait loci analysis, a potential association was seen between different genotypes of rs6576457 and miRNA-4508 expression (p=0.068) in 60 healthy individuals with exposure to silica dust.

“The detailed mechanism of action of this miRNA remains to be elucidated,” the investigators noted.