In silico study of the genetic basis of radiation dermatitis: a route for the discovery of potential therapeutic targets

Abstract

Radiation therapy along with surgery and chemotherapy are the main general treatment options for cancer patients. Besides, radiation dermatitis (RD) is considered the most common side effect that affects mutually the physiology of the skin and the cancer therapy scheme. Multiple studies of genetic influence in several skin pathologies such as atopic dermatitis, psoriasis and vitiligo have revealed common target genes such as XRCC1, XRCC3, XPD, MLH1, MSH2, RAD51 and others, which have been also reported to be related to RD´s occurrence in patients of certain types of cancers. However, the genetic influence associated with this pathology remains largely unknown. The objective of this study is to evaluate the genetic make-up of radiation dermatitis via bioinformatic tools to identify the most relevant genes and subsequently correlate these findings with gene expression analysis. We conducted a literature search to identify the most relevant genes related to radiation dermatitis according to the most recent studies. Then, using bioinformatic tools, we assembled a genetic network for radiation dermatitis and analyzed the relevance and influence of identified genes within the network. Then, using samples available from GEO public database, we carried out a gene expression analysis. This process was repeated for atopic dermatitis for comparison purposes. Our findings indicate that the physiological pathways of radiation dermatitis involve several genes related to DNA repair processes such as XRCC, RAD51, and BRCA2. Also, genes connected to inflammatory responses such as CCL2, CXC4, and IL1. Finally, dysregulation in genes such as PLG and EGFR involved in healthy tissues and physiological skin processes represent potential therapeutic targets for this disease.