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

Background: 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.

Aims: 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.

Patients/methods: 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.

Results: 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.

Conclusion: 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.