Analysis of Keloid Response to 5-Fluorouracil Treatment and Long-Term Prevention of Keloid Recurrence.

Keloids are benign fibroproliferative skin tumors which can cause disfigurement and disability. While they frequently recur after excision or medical management and can affect 6-16% of African Americans, there is no gold standard therapy. Keloids are challenging to study because there are no animal or in vitro models of this disorder. This makes it very difficult to validate data from treated tissue samples or cells and develop targeted therapies for this disease. In this study, we demonstrate that intralesional 5-FU injection after keloid excision prevents recurrence for 2 years with no reported adverse events. We analyze the expression of treated and untreated biopsies of the same keloids in their native context to capture insights which may be missed by in vitro cell culture models and correct for intra-keloid variability. Random Forest analysis of the microarray data dramatically increased the statistical power of our results; permitting hypothesis-free creation of a gene expression profile of 5-FU treated keloids. Through this analysis, we found a set of genes, including YAP1 and CCL-2, whose expression changes predicts 5-FU therapy status and includes genes which have not previously been associated with keloid biology and of unknown function. We further described keloid heterogeneity for the first time using multidimensional analysis of our microarray results. The methods and tools we developed in this research may overcome some of the challenges in studying keloids and developing effective treatments for this disease. Financial disclosure agreement: None of the authors have any financial arrangements or potential conflicts of interest related to this article. Acknowledgements: This work was funded by (TL1TR001104) for RL. This study was supported by NIH 2R01LM009254 and 2R01LM008111 for AKF. Corresponding author: Tae Chong, MD, University of Colorado Department of Surgery, Division of Plastic Surgery, 12631 East 17th Ave, Rm 6417, Denver, CO 80045, tae.chong@ucdenver.edu ©2018American Society of Plastic Surgeons

https://ift.tt/2QBH1hJ