Relationship between BAP1, FOXO3 and ITPR2 gene expression and metastasis and prognosis of uveal melanoma / 中华实验眼科杂志

ABSTRACT

Objective:To explore the potential biomarkers for the metastasis and prognosis of uveal melanoma (UM) from molecular genetics.Methods:The data of 80 UM samples including 18 metastatic cases and 62 non-metastatic cases between 2007 and 2019 were downloaded from The Cancer Genome Atlas database.The tumor mutation burden and gene mutation information, including mutant genes, variant type, the proportion of single nucleotide variation (SNV) and mutation proportion, were analyzed using maftools package in R software, and the differentially expressed genes (DEGs) between the two groups were screened using edgeR package.The Kyoto Encyclopedia of Genes and Genomes enrichment analysis based on the DEGs was performed to screen prognosis-associated genes using KOBAS.Cox regression model was established using survival package in R software to verify the association between gene mutation and DEGs and the prognosis of UM patients.Results:The mutation analysis showed that missense mutation accounted for a large proportion in the mutation of UM samples, and the main variant type was SNV, and the mutation burden of UM was low.Compared with the non-metastatic UM samples, 562 DEGs were identified in the metastatic UM samples.Three pathways, including vitreoretinal degeneration, proteoglycans in cancer, and PI3K-Akt pathway, were significantly enriched.The expression levels of BAP1, FOXO3 and ITPR2 were 2 982.50 (1 251.50, 5 637.00), 1 223.00 (914.75, 2 706.25) and 2 201.50 (570.75, 4 814.00)in the metastatic group, and 5 225.00 (2 281.25, 8 784.00), 2 293.50 (1 254.25, 3 693.75) and 474.00 (153.00, 1 437.75) in the non-metastatic group, respectively.The expression of BAP1 and FOXO3 among the DEGs were significantly down-regulated and ITPR2 expression was significantly up-regulated in the metastatic group in comparison with the non-metastatic group ( Z=-1.786, -1.982, -3.065; all at P<0.10). The survival analysis revealed BAP1 mutation, decreased FOXO3 expression and increased ITPR2 expression were associated with inferior survival of UM patients (all at P<0.10). Conclusions:BAP1 mutation, up-regulation of FOXO3 and down-regulation of ITPR2 might be potential biomarkers for the metastasis and prognosis of UM.