Identification of hub genes related to silicone-induced immune response in rats

// Xiaolu Huang 1, * , Yiwen Zhou 1, * , Wenhui Liu 1 , Haizhou Li 1 , Xiao Liang 1 , Rui Jin 1 , Hengyu Du 1 , Jizhou He 1 , Bangda Chai 1 , Ran Duan 1 and Qingfeng Li 1 1 Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R.China * These authors contributed equally to this work and should be considered as co-author Correspondence to: Qingfeng Li, email: dr.liqingfeng@shsmu.edu.cn Keywords: silicone implant, autoimmunity, microarray, WGCNA, hub genes Received: July 04, 2017 Accepted: September 21, 2017 Published: October 06, 2017 ABSTRACT Silicone implants are used widely in the field of plastic surgery and are used in a large population. However, their safety profile, especially the silicone-induced immune response, has been a major concern for plastic surgeons for decades. It has been hypothesized that there is a cause and effect relation between silicone and immunity, but this is controversial. The objective of the present study was to determine the hub genes and key pathways related to silicone implant–induced immune responses in a rat model. In addition to cluster and enrichment analyses, we used weighted gene co-expression network analysis (WGCNA) to examine the gene expression profiles in a systematic context. A total five genes ( Fes , Aif1 , Gata3 , Tlr6 , Tlr2 ) were identified as hub genes that are most likely related to the silicone-induced immune response, four of which ( Aif1 , Gata3 , Tlr6 , Tlr2 ) have been associated with autoimmunity as target genes or disease markers. The Toll-like receptor signaling pathway ( p < 0.01, fold enrichment: 7.01) and systemic lupus erythematosus signaling pathway ( p < 0.05, fold enrichment: 5.01), which are considered strongly associated with autoimmunity, were significantly enriched in the silicone-implanted skin samples. The results indicate that silicone implants might trigger the localized immune response, as various immune reaction genes were detected after silicone implantation. The identified five hub genes will hopefully serve as novel therapeutic targets for silicone-related complications and the associated autoimmune diseases.