Peptidase inhibitor 3 and chemokine ligand 27 may serve as biomarkers for actinic keratoses in organ transplant recipients

Eur J Dermatol. 2019 Jun 1;29(3):259-267. doi: 10.1684/ejd.2019.3559.

Abstract

Molecular profiling of tissue samples in organ transplant recipients (OTRs) may allow early and minimally invasive identification of actinic keratosis (AK). The aim of this study was to compare mRNA expression profiles of 13 genes, as putative genetic biomarkers of AK, before and after treatment using two different field therapies, and to correlate the results with histological and clinical parameters. For this single-centre prospective randomized intra-patient-controlled study, 10 OTRs with AKs were recruited for field therapy with two cycles of methyl-5-aminolevulinate 16% cream-photodynamic therapy (PDT) at one site and imiquimod 5% cream for four weeks at another site. AKs in the PDT area were reduced significantly at one, two, and six months after completion of the treatment (p < 0.001). The effect of imiquimod was weaker but still significant when evaluated during the same intervals (p < 0.001). By comparing the mRNA expression profiles of various genetic markers before, during, and three months after therapy, we observed specific patterns of expression for skin-derived peptidase inhibitor 3 (PI3) and chemokine ligand 27 (CCL27) in all groups, regardless of the treatment modality. Compared to healthy skin, the expression of PI3 was strongly decreased and that of CCL27 increased in AK lesions before therapy. The expression level of both genes showed a significant convergence to values observed in healthy skin in both groups after therapy. The pattern and level of specific gene expression in actinic keratoses could serve as a biomarker.

Keywords: actinic keratosis; photodynamic therapy; skin markers.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Topical
  • Aged
  • Aminolevulinic Acid / administration & dosage
  • Aminolevulinic Acid / analogs & derivatives*
  • Biomarkers / analysis
  • Chemokine CCL27 / genetics
  • Elafin / genetics
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation
  • Humans
  • Imiquimod / administration & dosage*
  • Keratosis, Actinic / drug therapy*
  • Keratosis, Actinic / genetics*
  • Keratosis, Actinic / pathology
  • Male
  • Middle Aged
  • Photochemotherapy / methods*
  • Prospective Studies
  • RNA, Messenger / genetics
  • Reference Values
  • Severity of Illness Index
  • Transplant Recipients
  • Treatment Outcome

Substances

  • Biomarkers
  • Chemokine CCL27
  • Elafin
  • PI3 protein, human
  • RNA, Messenger
  • methyl 5-aminolevulinate
  • Aminolevulinic Acid
  • Imiquimod