A Novel Four Genes of Prognostic Signature for Uveal Melanoma

Abstract

Autophagy and immunity play critical roles in various cancers, but the prognostic impact of autophagy and immunity for uveal melanoma (UM) remains lacking. Therefore, the RNA sequencing of data in the TCGA-UVM dataset was downloaded from UCSC Xena database. The prognostic autophagy- and immunity-related genes (AIRGs) were selected via univariate Cox regression. Next, we applied LASSO method to construct four genes of signature in the TCGA-UVM and verified in another two GEO datasets (GSE84976 and GSE22138). This signature intimately associated with overall survival (OS) time and metastasis-free survival (MFS) time of UM, which could be considered as a prognostic indicator. Besides, by applying risk assessment, the patients of UM can be divided into two subgroups (high/low risk) with different survival time, distinct clinical outcomes, and immune microenvironments. Gene set enrichment analysis (GSEA) manifested that cancer hallmark epithelial-mesenchymal transition and KRAS pathways were positively activated in the high-risk group. Moreover, the high-risk group could be more sensitive to chemotherapies than the low-risk group. Thus, our finding suggested that the four genes of signature closely linked with UM risk and survival can afford more accurate survival prediction and potential therapeutic targets for clinical application.

The Role of Autophagy in Human Uveal Melanoma and the Development of Potential Disease Biomarkers and Novel Therapeutic Paradigms

“…With increased UM patient data, this field of research will provide imperative information to the diagnostics and treatment paradigm of UM. By using the TCGA-UVM gene database then validating it with gene expression database (GSE84976, GSE 22138) Liu et al was able to successfully correlate autophagy and immune related genes to reveal four novel genes (PRKCD, MPL, EREG, and JAG2) in UM that has been correlated with prognosis in other malignancies [122]. The risk scores generated for the four genes are closely related to chromosome 3 status and was an accurate interpretation of patient prognosis when used in the three patient databases.…”

“…Further correlation identified immune changes such as fraction of CD4, CD8, regulatory T cell and NK cell activation, monocytes, macrophages M1, and mast cells in the high-risk score group to significantly differ from UM patients in the low-risk score group. Additionally, association between drug resistance of two common drug among the three database and risk score determined significant differences in drug sensitivity where high risk group could be more sensitive to chemotherapy [122].…”

Identification and validation of immunogenic cell death-related score in uveal melanoma to improve prediction of prognosis and response to immunotherapy

“…In addition, we retrieved mRNA risk models which had been constructed to predict the prognosis of UVM patients by searching the Pubmed website. After excluding some models with no formula available to calculate the risk score [34][35][36][37][38], 19 mRNA signatures (Supplementary Table 3) were finally enrolled to benchmark the ICDscore. These signatures were relevant to many biological processes, including immune cell infiltration [39,40], autophagy [41], DNA methylation [42], necroptosis [43], pyroptosis [44],…”

Role of a cuproptosis-related prognostic signature in uveal melanoma tumor microenvironment and immune responses

“…Uveal melanoma (UVM), the most prevalent primary intraocular malignancy, accounts for 70% of all ocular malignancies (Liu et al, 2022;Rantala et al, 2022). Although there have been signi cant advancements in the early identi cation and local oncologic therapy of UVM, metastases still occur in approximately 50% of patients, leaving them with a dismal prognosis (Carvajal et al, 2017;Fry et al, 2019).…”