Differential expression of NOTCH Signaling genes in tissue collected from hidradenitis suppurativa patients

Hidradenitis suppurativa (HS) is a morbid chronic inflammatory skin disease that can be treated at burn centers through surgical intervention. Despite multiple pathogenesis theories, the genetic basis of sporadic HS remains largely unknown. This study investigates differences in regulation of multiple genes between normal skin (NS) and HS samples in skin of color patients. RNA was isolated from NS and HS samples for 84 gene NOTCH signaling pathway PCR array analysis. qRT-PCR and protein quantification using immunofluorescence (IF) was also performed for 3 genes related to NOTCH signaling pathway: HEY1, NCSTN, and TRAIL. Demographic information was compared among patients that showed differential gene expression and those that did not. PCR array analysis of 12 NS and 21 HS samples found genes involved in embryological development, cell signaling and proliferation to be dysregulated in HS compared to NS. qRT-PCR and IF analysis showed HEY1, NCSTN, and TRAIL to be upregulated in 25%, 25% and 55% of HS samples, respectively. HS samples that had differential gene expression of Hey1 and NCSTN were more likely to derive from patients who did not smoke (p=.0109 and p=.0121, respectively). 18 out of 21 HS patients demonstrated differential gene expression for TRAIL (85.7%; t-test score 0.0009). Variable gene expression might explain the refractory nature of HS and variation in response to treatment modalities. Further research involves elucidating the precise role of NOTCH signaling in the pathogenesis of HS and exploring the potential for targeting NOTCH-related genes through pharmacologic approaches.