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.

Tumor infiltration, known to associate with various cancer initiations and progressions, is a promising therapeutic target for aggressive cutaneous melanoma. Then, the relative infiltration of 24 kinds of immune cells in melanoma was assessed by a single sample gene set enrichment analysis (ssGSEA) program from a public database. The multiple machine learning algorithms were applied to evaluate the efficiency of immune cells in diagnosing and predicting the prognosis of melanoma. In comparison with the expression of immune cell in tumor and normal control, we built the immune diagnostic models in training dataset, which can accurately classify melanoma patients from normal (LR AUC = 0.965, RF AUC = 0.99, SVM AUC = 0.963, LASSO AUC = 0.964, and NNET AUC = 0.989). These diagnostic models were also validated in three outside datasets and suggested over 90% AUC to distinguish melanomas from normal patients. Moreover, we also developed a robust immune cell biomarker that could estimate the prognosis of melanoma. This biomarker was also further validated in internal and external datasets. Following that, we created a nomogram with a composition of risk score and clinical parameters, which had high accuracies in predicting survival over three and five years. The nomogram’s decision curve revealed a bigger net benefit than the tumor stage. Furthermore, a risk score system was used to categorize melanoma patients into high- and low-risk subgroups. The high-risk group has a significantly lower life expectancy than the low-risk subgroup. Finally, we observed that complement, epithelial-mesenchymal transition, and inflammatory response were significantly activated in the high-risk group. Therefore, the findings provide new insights for understanding the tumor infiltration relevant to clinical applications as a diagnostic or prognostic biomarker for melanoma.

Background: Autophagy and immunity related genes serve crucial roles in carcinogenesis, but little is known about the prognostic impact for uveal melanoma (UM).Methods: Autophagy related and immunity related genes (AIRGs) expression data of 80 UM patients were obtained from the cancer genome atlas project (TCGA) database. Next, univariate cox regression analysis and the least absolute shrinkage and selection operator (LASSO) algorithms were applied to build a robust AIRGs signature in TCGA and validated in another two independent datasets. Besides, UM patients classified into two subgroups based on the risk model. Differences of clinical outcome, tumor microenvironment and the likelihood of chemotherapeutic response were further explored.Results: In total, a 4-AIRGs signature was constructed and validated in various datasets, which can robustly predict patients’ metastasis-free survival (MFS) and overall survival (OS) and is an independent prognostic factor in UM. The UM patients can be classified into high and low risk subgroups by applied risk score system. The high risk group have poor clinical outcomes, higher CD8+ T cell and macrophage immune-infiltrating and more sensitive to chemotherapies. In addition, Gene Set Enrichment Analysis (GSEA) analysis revealed that hallmark epithelial-mesenchymal transition and KRAS pathways are commonly enriched in high-risk expression phenotype.Conclusion: Thus, our findings provide a new clinical strategy for the accurate diagnosis and identify a novel prognostic autophagy and immunity associated biomarker for the treatment of uveal melanoma.