Identification of differentially expressed genes in actinic keratosis samples treated with ingenol mebutate gel

Abstract

Actinic keratosis is a common skin disease that may progress to invasive squamous cell carcinoma if left untreated. Ingenol mebutate has demonstrated efficacy in field treatment of actinic keratosis. However, molecular mechanisms on ingenol mebutate response are not yet fully understood. In this study, we evaluated the gene expression profiles of actinic keratosis lesions before and after treatment with ingenol mebutate using microarray technology. Actinic keratoses on face/scalp of 15 immunocompetent patients were identified and evaluated after treatment with topical ingenol mebutate gel 0.015%, applied once daily for 3 consecutive days. Diagnostic and clearance of lesions was determined by clinical, dermoscopic, and reflectance confocal microscopy criteria. Lesional and non-lesional skin biopsies were subjected to gene expression analysis profiled by Affymetrix microarray. Differentially expressed genes were identified, and enrichment analyses were performed using STRING database. At 8 weeks post-treatment, 60% of patients responded to ingenol mebutate therapy, achieving complete clearance in 40% of cases. A total of 128 differentially expressed genes were identified following treatment, and downregulated genes (114 of 128) revealed changes in pathways important to epidermal development, keratinocyte differentiation and cornification. In responder patients, 388 downregulated genes (of 450 differentially expressed genes) were also involved in development/differentiation of the epidermis, and immune system-related pathways, such as cytokine and interleukin signaling. Cluster analysis revealed two relevant clusters showing upregulated profile patterns in pre-treatment actinic keratoses of responders, as compared to non-responders. Again, differentially expressed genes were mainly associated with cornification, keratinization and keratinocyte differentiation. Overall, the present study provides insight into the gene expression profile of actinic keratoses after treatment with ingenol mebutate, as well as identification of genetic signatures that could predict treatment response.

FOXA1 repression drives lineage plasticity and immune heterogeneity in bladder cancers with squamous differentiation

“…3a ; Fold Change >2 and FDR < 0.05). A subset of the genes upregulated in the SqD regions were genes previously reported to be highly expressed in squamous carcinomas of various lineages, including the peptidase kallikrein genes KLK13 26 , KLK10 27 , and KLK12 28 , the cornification-related genes CNFN and PLA2G4E 29 , the small proline-rich protein genes SPRR2D and SPRR2E 30 , the keratin genes KRT16 31 , KRT31 32 and KRTDAP 33 , the interleukin IL36G 34 , and the desmogleins DSG1/3/4 and desmocollins DSC2/3 35 , 36 ( Fig. 3b ) .…”

Preliminary Evidence of Efficacy, Safety, and Treatment Satisfaction with Tirbanibulin 1% Ointment: A Clinical Perspective on Actinic Keratoses

“…Even the topical medical device piroxicam 0.8% with sunscreen filters favors a regression of grade I and II AKs with good outcomes. Its use could be considered to treat FC, as documented in numerous clinical real-life studies and also in transplant patients or in those taking photosensitizers antihypertensives drugs [20][21][22][23][24]. Preventive therapy of AKs, on the other hand, is mainly based on photo sunscreen [25].…”