Tell-Marti, G. | bioRxiv Science

bioRxiv2025

Transcriptomic meta-analysis in plaque psoriasis: an integrative bioinformatic approach to deciphering the genetic landscape and molecular pathways

Psoriasis is a chronic inflammatory skin disease influenced by both genetic and environmental factors. Despite extensive research, its precise etiology remains unclear, posing significant challenges to understanding and treatment. The disease pathogenesis involves self-reactive T cells and immune-related cytokines. Genome-wide association studies have identified various susceptibility loci for immune-related diseases, but the underlying mechanisms remain only partially understood. Recent discoveries of critical signaling pathways, biological processes, and immune cell involvement have expanded our knowledge and offer hope for improved therapeutic strategies. This study aimed to enhance our understanding of psoriasis and proposes novel therapeutic approaches by employing integrated bioinformatics to identify signaling pathways and biological processes as potential disease markers. Presenting a systematic review and taking a meta-analytical approach to transcriptomic profiles, this investigation examined differential gene expression patterns across 44 studies involving 975 samples comparing lesional psoriasis, non-lesional psoriasis, and healthy controls. Consensus transcriptome signatures revealed a significant association between immune-related genes and psoriasis pathogenesis. Functional enrichment analysis identified several enriched pathways related to immunity and immune system processes. Comparison of these findings with the existing literature indicated that some immune-related genes were already known, while others are novel in the context of psoriasis. Additionally, novel gene analysis demonstrated psoriasis involvement in pathways such as gluconeogenesis, the FoxO signaling pathway, and mitophagy. This integrative approach confirmed classic genetic associations while uncovering novel gene expression patterns and pathways relevant to psoriasis. Notably, the disruption of the gluconeogenesis pathway emerged as a critical finding. These insights enhance our understanding of psoriasis pathophysiology and pave the way for targeted therapies, offering improved management options for affected individuals.

molecular biology↗

bioRxiv2019

Inherited duplications of PPP2R3B promote naevi and melanoma via a novel C21orf91-driven proliferative phenotype

The majority of the heredity of melanoma remains unexplained, however inherited copy number changes have not yet been systematically studied. The genetic environment is highly relevant to treatment stratification, and new gene discovery is therefore desirable. Using an unbiased whole genome screening approach for copy number we identify here a novel melanoma predisposing factor, familial duplications of gene PPP2R3B, encoding a regulatory unit of critical phosphatase PP2A. Significant correlation between expression of PPP2R3B in tumour tissue and survival in a large melanoma cohort was confirmed, and associated with a non-immunological expression profile. Mechanistically, construction and extensive characterization of a stable, inducible cellular model for PPP2R3B overexpression revealed induction of pigment cell switching towards proliferation and away from migration. Importantly, this was independent of the known microphthalmia-associated transcription factor (MITF)-controlled pigment cell phenotype switch, and was instead driven by uncharacterised gene C21orf91. Bioinformatic studies point to C21orf91as a novel target of MITF, and therefore a potential hub in the control of phenotype switching in melanoma. This study identifies novel germline copy number variants in PPP2R3B predisposing to melanocytic neoplasia, and uncovers a new potential therapeutic target C21orf91 in the control of pigment cell proliferation.

genomics↗