PLX138464

GSE148387: Transcriptional Characterization of the Tumor Microenvironment and Prognostic Gene Signatures in Conjunctival Melanoma

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Purpose: To characterize the transcriptome and cellular the tumor microenvi-ronment of conjunctival melanoma (CM) compared to healthy conjunctiva and to analyze the transcriptional differences between CM with good and poor clinical outcome.; Methods: Twelve formalin-fixed and paraffin-embedded (FFPE) CM of twelve patients were analyzed by Massive Analysis of cDNA Ends (MACE) RNA se-quencing. Six samples each with good and poor clinical outcome were exam-ined, the latter being defined by local recurrence or systemic metastases with a follow-up of at least 24 months. Eight age-matched healthy FFPE conjunctival specimens from eight patients who underwent retinal detachment surgery served as controls. Bioinformatic cell type enrichment analysis with xCell was used to characterize the tumor microenvironment (TME). Differentially expressed genes (DEG) and the associated biological processes were analyzed between CM and control conjunctiva. Additionally, a prognostic transcription profile was identified by comparing melanoma of good and poor clinical outcome.; Results: The TME of conjunctival melanoma was characterized by the enrich-ment of melanocytes, pericytes and especially several immune cell types. Among them, plasmacytoid dendritic cells (pDC), natural killer T cells (NKT), B cells and mast cells were most significantly increased in CM compared to healthy conjunc-tiva. DEG between CM and control were mainly involved in biological processes such as inhibition of apoptosis, proteolysis and response to growth factors. POU3F3, BIRC5 and 7 were among the top expressed genes associated with inhibition of apoptosis. Twenty genes, among them CENPK, INHA, USP33 and CASP3, were identified as prognostically relevant factors reaching high classifi-cation accuracy (AUC: 1.0).; Conclusions: The present study provides new insights into the TME and the transcriptional profile of CM and additionally identifies new prognostic bi-omarkers. These results might lead to new diagnostic and therapeutic options for CM. SOURCE: Clemens Lange Uniklinik Freiburg