Anti-IL17C (full length) polyclonal antibody

Background: Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer, and inflammation relates significantly to its initiation and prognosis. Systematic exploration of the immunogenomic landscape therein to assist in PTC prognosis is therefore urgent. The Cancer Genome Atlas (TCGA) project provides a large number of genetic PTC samples that enable a comprehensive and reliable immunogenomic study. Methods: We integrated the expression profiles of immune-related genes (IRGs) and progression-free intervals (PFIs) in survival in 493 PTC patients based on the TCGA dataset. Differentially-expressed and survival-associated IRGs in PTC patients were estimated a computational difference algorithm and COX regression analysis. The potential molecular mechanisms and properties of these PTC-specific IRGs were also explored with the help of computational biology. A new prognostic index based on immune-related genes was developed by using multivariable COX analysis. Results: A total of 46 differentially expressed immune-related genes were significantly correlated with clinical outcome of PTC patients. Functional enrichment analysis revealed that these genes were actively involved in a cytokine-cytokine receptor interaction KEGG pathway. A prognostic signature based on IRGs (AGTR1, CTGF, FAM3B, IL11, IL17C, PTH2R and SPAG11A) performed moderately in prognostic predictions, and correlated with age, tumor stage, metastasis, number of lesions, and tumor burden. Intriguingly, the prognostic index based on IRGs reflected infiltration by several types of immune cells. Conclusions: Together, our results screened several IRGs of clinical significance, revealed drivers of the immune repertoire, and demonstrated the importance of a personalized, IRG-based immune signature in the recognition, surveillance, and prognosis of PTC.

Background: NIPAL4, encoding the NIPA-like domain containing 4 protein (NIPAL4), is one of the causative genes of autosomal recessive congenital ichthyosis (ARCI). The physiological role of NIPAL4 and the pathogenetic mechanisms of ARCI caused by NIPAL4 mutations remain unclear. Objective: To clarify the changes of ceramide components in the lesional stratum corneum (SC) and the gene expression profile in the lesional skin of an ARCI patient with a novel frameshift mutation in NIPAL4. Methods: We performed ultrastructural and immunohistochemical analyses of the skin. We used RNA sequencing to determine the mRNA expression in the skin of the patient and healthy individuals. We investigated ceramide components using tape stripped SC samples from the patient. Results: mRNA expression profiling in the patient's skin showed significant upregulation of IL-17/TNF alpha-related genes (IL17C, IL36A, IL36G, S100A7A, S100A9) and psoriasis hallmark genes (VNN3, LCE3D, PLA2G4D), and significant downregulation of lipid-associated genes (GAL, HAO2, FABP7). Ceramide analysis in the patient's SC revealed amounts of CER[NS] with carbon chain-length (C) 32-52 were increased, while amounts of most acylceramide with C66:2- C72:2 were reduced relatively to those in healthy individuals. After the retinoid treatment, CER[NS] with carbon chains C46-54, CER[E01-1] and CER [EOP] increased. Conclusion: IL-17C and IL-36 family cytokines might be involved in the pathogenetic process of ARCI with NIPAL4 mutations. Reduced amounts of the acylceramides in the SC are associated with the skin phenotype due to NIPAL4 mutations. Efficacy of the oral retinoid treatment might be due to restored amounts of CERIEOHI and CER[EOP] in the SC. (C) 2019 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.