Transcriptome comparison of isotretinoin-effective and isotretinoin-ineffective severe acne vulgaris patients.

Abstract

Oral isotretinoin is the first-line treatment of severe nodular acne. However, patients presenting ineffective or poor effective to oral isotretinoin are still a clinical problem, and its molecular genetic mechanisms remain unclear. To compare the transcriptome profiles of isotretinoin-effective and isotretinoin-ineffective severe acne vulgaris patients and analyze the potential physiological roles to better understand the mechanisms of isotretinoin efficacy differences. Peripheral blood of 43 patients with severe acne was collected before treatment. After 8-week isotretinoin, patients presented effective and ineffective to isotretinoin treatment were selected and their pretreatment peripheral blood was analyzed. High-throughput sequencing was used to detect gene expression profiles. Gene Ontology and KEGG were used to perform functional annotation and pathway enrichment analysis. Ten acne patients (3 male and 7 female, age 31±9.2) presented effectiveness by oral isotretinoin and 10 acne patients (4 male and 6 female, age 28±7.7) presented ineffectiveness were included. Comparison of gene profiles of isotretinoin-effective and isotretinoin-ineffective patients revealed 2779 differentially expressed genes: 2723 upregulated and 56 downregulated. Differentially expressed genes were enriched in RNA degradation pathway, autophagy pathway, protein ubiquitination pathway, protein processing in endoplasmic reticulum pathway, T-cell receptor signaling pathway, spliceosome pathway, mRNA surveillance pathway, cell cycle pathway, long-term potentiation pathway, and FoxO signaling pathway. Transcriptome expression differences not only participated in the acne pathogenesis, but also influenced the isotretinoin therapeutic effects. These findings might provide some evidence for exploring individualized therapy for acne patients.