PRRX1 Is a Novel Prognostic Biomarker and Facilitates Tumor Progression Through Epithelial–Mesenchymal Transition in Uveal Melanoma

Abstract

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UM develops and is sustained by inflammation and immunosuppression from the tumor microenvironment (TME). This study sought to identify a reliable TME-related biomarker that could provide survival prediction and new insight into therapy for UM patients. Based on clinical characteristics and the RNA-seq transcriptome data of 80 samples from The Cancer Genome Atlas (TCGA) database, <i>PRRX1</i> as a TME- and prognosis-related gene was identified using the ESTIMATE algorithm and the LASSO-Cox regression model. A prognostic model based on <i>PRRX1</i> was constructed and validated with a Gene Expression Omnibus (GEO) dataset of 63 samples. High <i>PRRX1</i> expression was associated with poorer overall survival (OS) and metastasis-free survival (MFS) in UM patients. Comprehensive results of the prognostic analysis showed that <i>PRRX1</i> was an independent and reliable predictor of UM. Then the results of immunological characteristics demonstrated that higher expression of <i>PRRX1</i> was accompanied by higher expression of immune checkpoint genes, lower tumor mutation burden (TMB), and greater tumor cell infiltration into the TME. Gene set enrichment analysis (GSEA) showed that high <i>PRRX1</i> expression correlated with angiogenesis, epithelial-mesenchymal transition (EMT), and inflammation. Furthermore, downregulation of <i>PRRX1</i> weakened the process of EMT, reduced cell invasion and migration of human UM cell line MuM-2B <i>in vitro</i>. Taken together, these findings indicated that increased <i>PRRX1</i> expression is independently a prognostic factor of poorer OS and MFS in patients with UM, and that <i>PRRX1</i> promotes malignant progression of UM by facilitating EMT, suggesting that <i>PRRX1</i> may be a potential target for UM therapy.