The prognostic value of immune-related genes AZGP1, SLCO5A1, and CTF1 in Uveal melanoma

Abstract

ObjectiveUveal melanoma (UM) is an aggressive malignancy with a poor prognosis and no available effective treatment. Therefore, exploring a potential prognostic marker for UM could provide new possibilities for early detection, recurrence, and treatment.MethodsIn this study, we used “ConsensusClusterPlus” to classify patients with UM into subgroups, screened for significant differences in immune prognostic factors between subgroups, selected three genes using LASSO (Least absolute shrinkage and selection operator) regression to construct a risk model, and performed tumor immune cell infiltration analysis on the risk model. infiltration analysis, and then verified the heterogeneous role of the 3 core genes in other cancers by pan-cancer analysis and validate its expression by RT-qPCR in normal and tumor cells.ResultsWe consistently categorized 80 UM patients into two subgroups after the immunogenetic set, where the UM1 subgroup had a better prognosis than the UM2 subgroup, and used 3 immune-related genes AZGP1, SLCO5A1, and CTF1 to derive risk scores as independent prognostic markers and predictors of UM clinicopathological features. We found significant differences in overall survival (OS) between low- and high-risk groups, and prognostic models were negatively correlated with B cell and myeloid dendritic cell and positively correlated with CD8+ T cell AZGP1 and CTF1 were significantly upregulated in UM cells compared with normal UM cells.ConclusionImmunogens are significantly associated with the prognosis of UM, and further classification based on genetic characteristics may help to develop immunotherapeutic strategies and provide new approaches to develop customized treatment strategies for patients.

Machine Learning Methods for Gene Selection in Uveal Melanoma

“…ACSF2 was found to be among ferroptosis regulators in a signature, used to distinguish UM patients with different overall survival, that defined two clusters of patients with differences in prognosis and tumor-microenvironment-infiltrating cells [28,29]. CTF1 has been part of a previously defined UM-immune-related three-gene signature on TCGA data [30]. CARD11 was detected as a prognostic marker, with high expression associated to poor OS in the TCGA UVM dataset; in particular, metastatic patients had higher expression of this gene [31]; however, the MGS based on a larger dataset [17] assigned a protective effect to this gene, probably due to a set of patients with limited survival, metastatic disease and low CARD11 expression (Figures S2 and S3).…”

“…Other genes such as PLXNB1 and HLA-A were part of an immune gene signature used to define two risk classes, one of which had higher immune cell infiltration and lower survival in the TCGA UVM dataset [35]. CTF1 and RAPGEF3 were previously reported to be parts of gene signatures related to tumor microenvironment and immune system [26,30], with the first seen downregulated and methylated in BAP1 mutated samples [36]; PALMD was found to have low expression in metastatic UM tissues [37], and GSTA3 in low-survival patients [38].…”