Tissue-engineered human psoriatic skin supplemented with cytokines as an in vitro model to study plaque psoriasis
Authors: Pouliot-Berube, Claudia; Zaniolo, Karine; Guerin, Sylvain L.; Pouliot, Roxane
Aim: Psoriasis is a chronic inflammatory skin disease. To study its complex etiology, a psoriatic skin substitute model supplemented with a cytokine cocktail has been used. Materials & methods: Reconstructed psoriatic skin substitutes were supplemented with a cocktail of four cytokines: TNF-alpha, IL-1 alpha, IL-6 and IL-17A, to monitor their impact on gene expression by DNA microarray. Results: Gene profiling analyses identified several deregulated genes reported as being also deregulated in psoriasis skin in vivo (S100A12, IL-8, DEFB4A and KYNU). The expression of those genes was dramatically increased compared with basal levels of controls (p < 0.005 to < 0.05). Conclusion: Psoriatic substitutes supplemented with a cocktail of TNF-alpha, IL-1 alpha, IL-6 and IL-17A showed similar transcriptome alterations to those found in psoriasis.
DEFB4A is a potential prognostic biomarker for colorectal cancer
Authors: Wu, Qian; Wang, Dan; Zhang, Zhen; Wang, Yaping; Yu, Weina; Sun, Kai; Maimela, Nomathamsanqa Resegofetse; Sun, Zhenqiang; Liu, Jinbo; Yuan, Weitang; Zhang, Yi
Colorectal cancer (CRC) is the third leading cause of cancer-associated mortality. The present study aimed to investigate novel biomarkers to predict prognosis and provide a theoretical basis for studies of the pathogenesis and the development of therapies for CRC. The present study compared mRNA expression levels of patients with CRC with short- and long-term prognosis and of individuals with and without tumors in The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were identified via volcano plot and Venn diagram analysis. Gene Ontology (GO) analysis and gene set enrichment analysis (GSEA) were performed to identify the functions of the DEGs, and the DEGs were further verified using clinical CRC samples. A total of 10 DEGs were identified as candidate genes using the TCGA database, and four DEGs [defensin beta 4A (DEFB4A), hyaluronan binding protein 2 (HABP2), oleoyl-ACP hydrolase and TBC1 domain family member 3G] were associated with poor prognosis of patients with CRC. Two DEGs (DEFB4A and HABP2) were upregulated in tumor tissues of patients with CRC in the TCGA database. GO and GSEA analyses revealed that DEFB4A was highly associated with immunosuppression, participates in 'myeloid leukocyte differentiation', 'leukocyte proliferation' and 'positive regulation of leukocyte-mediated immunity', and was positively correlated with CD11b, CD14, CD45, CD163 and IL17A. Furthermore, DEFB4A expression was significantly upregulated in patients with large tumors, advanced cancer stage, lymph node metastasis and liver metastasis. Survival analysis revealed that DEFB4A upregulation was associated with poor prognosis. DEFB4A gene knockdown experiments demonstrated that DEF4BA promotes cell migration. These results indicated that DEFB4A potentially promotes tumor growth by regulating immunosuppressive activity and provided novel insights into the diagnosis and treatment of CRC.