Identification of prognostic genes in uveal melanoma microenvironment

Abstract

Background: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Many previous studies have demonstrated that the infiltrating of immune and stromal cells in the tumor microenvironment contributes significantly to prognosis.

Methods: Dataset TCGA-UVM, download from TCGA portal, was taken as the training cohort, and GSE22138, obtained from GEO database, was set as the validation cohort. ESTIMATE algorithm was applied to find intersection differentially expressed genes (DEGs) among tumor microenvironment. Kaplan-Meier analysis and univariate Cox regression model were performed on intersection DEGs to initial screen for potential prognostic genes. Then these genes entered into the validation cohort for validation using the same methods as that in the training cohort. Moreover, we conducted correlation analyses between the genes obtained in the validation cohort and the status of chromosome 3, chromosome 8q, and tumor metastasis to get prognosis genes. At last, the immune infiltration analysis was performed between the prognostic genes and 6 main kinds of tumor-infiltrating immune cells (TICs) for understanding the role of the genes in the tumor microenvironment.

Results: 959 intersection DEGs were found in the UM microenvironment. Kaplan-Meier and Cox analysis was then performed in the training and validation cohorts on these DEGs, and 52 genes were identified with potential prognostic value. After comparing the 52 genes to chromosome 3, chromosome 8q, and metastasis, we obtained 21 genes as the prognostic genes. The immune infiltration analysis showed that Neutrophil had the potential prognostic ability, and almost every prognostic gene we had identified was correlated with abundances of Neutrophil and CD8+ T Cell.

Conclusions: Identifying 21 prognosis genes (SERPINB9, EDNRB, RAPGEF3, HFE, RNF43, ZNF415, IL12RB2, MTUS1, NEDD9, ZNF667, AZGP1, WARS, GEM, RAB31, CALHM2, CA12, MYEOV, CELF2, SLCO5A1, ISM1, and PAPSS2) could accurately identify patients' prognosis and had close interactions with Neutrophil in the tumor environment, which may provide UM patients with personalized prognosis prediction and new treatment insights.