PTEN Hypomethylation Could Be A Biomarker For Early Detection of Silicosis

Abstract

The overwhelming majority of subjects in current silicosis mRNA and miRNA expression profile are of human blood, lung cell, or rats model, which put limit on understanding of silicosis pathogenesis and therapy. It is essential to identify differentially expressed mRNAs and miRNAs profiles in silicosis patients lung tissues, and explore potential biomarker for early detection of silicosis. So we conducted a transcriptome study based on fifteen silicosis patients and eight normal people lung tissues, meanwhile, we validated the predictions with 404 silicosis patients and 177 normal people blood samples. The results showed that 1417 and 241 differentially expressed mRNAs and miRNAs were identified, respectively, among normal people, early stage silicosis, and advanced silicosis lung tissues (all P values < 0.05), whereas there were no significant difference in most mRNAs or miRNAs expression between early stage and advanced stage silicosis lung tissues. Enrichment analysis indicated phagosome, ribosome, olfactory transduction, antigen processing and presentation and PI3K-Akt pathways were mainly involved in the onset of silicosis. Series test of cluster (STC) analysis segregated differentially expressed mRNAs and miRNAs into five and three expressopm profiles patterns, repectively, with significant trends (P < 0.05), meanwhile, ten mRNAs (PIK3R3, KRAS, CTNNB1, HIF1A, ITGA2, KIT, SOCS3, GNAI3, STAT3 and PTEN) and nine miRNAs (hsa-miR-27a-3p, hsa-miR-27b-3p, hsa-miR-34b-3p, hsa-miR-3613-3p, hsa-miR-575, hsa-miR-8063, hsa-miR-937-5p, hsa-miR-181a-5p and hsa-miR-181b-5p) in patterns with opposite trends were selected to make further RT-qPCR validation in lung tissues and blood samples. Finally, the lung tissues RT-qPCR results verified microarray analyses of mRNAs and miRNAs expression trends, except for hsa-miR-575, hsa-miR-8063, and hsa-miR-937-5p, whereas blood samples RT-qPCR results PTEN and GNAI3 had opposite expression trends to those of lung tissues, and PTEN was identified as potential biomarker for silicosis early detection due to low methylation in the blood.