An autophagy-related prognostic signature associated with immune microenvironment features of uveal melanoma.

Autophagy is involved in cancer initiation and progression but its role in uveal melanoma (UM) was rarely investigated. Herein, we built an autophagy-related gene (ARG) risk model of UM patients by univariate Cox regression and least absolute shrinkage and selection operator (Lasso) regression model and filtrated out nine prognostic ARGs in The Cancer Genome Atlas (TCGA) cohort. Survival and Receiver Operating Characteristic (ROC) Curve analysis in the TCGA and other four independent UM cohorts (GSE22138, GSE27831, GSE44295 and GSE84976) proved that the ARG-signature possessed robust and steady prognosis predictive ability. We calculated risk scores for patients included in our study and patients with higher risk scores showed worse clinical outcomes. We found the expressions of the nine ARGs were significantly associated with clinical and molecular features (including risk score) and overall survival (OS) of UM patients. Furthermore, we utilized univariate and multivariate Cox regression analyses to determine the independent prognostic ability of the ARG-signature. Functional enrichment analysis showed the ARG-signature was correlated with several immune-related processes and pathways like T-cell activation and T-cell receptor signaling pathway. Gene set enrichment analysis (GSEA) found tumor hallmarks including angiogenesis, IL6-JAK-STAT3-signaling, reactive oxygen species pathway and oxidative phosphorylation were enriched in high-risk UM patients. Finally, infiltrations of several immune cells and immune-related scores were found significantly associated with the ARG-signature. In conclusion, the ARG-signature might be a strong predictor for evaluating the prognosis and immune infiltration of UM patients.

Zheng Z ，Zhang L ，Tu Z ，Deng Y ，Yin X ... -  《-》

A Comprehensive Prognostic and Immunological Analysis of a Six-Gene Signature Associated With Glycolysis and Immune Response in Uveal Melanoma.

Uveal melanoma (UM) is a subtype of melanoma with poor prognosis. This study aimed to construct a new prognostic gene signature that can be used for survival prediction and risk stratification of UM patients. In this work, transcriptome data from the Molecular Signatures Database were used to identify the cancer hallmarks most relevant to the prognosis of UM patients. Weighted gene co-expression network, univariate least absolute contraction and selection operator (LASSO), and multivariate Cox regression analyses were used to construct the prognostic gene characteristics. Kaplan-Meier and receiver operating characteristic (ROC) curves were used to evaluate the survival predictive ability of the gene signature. The results showed that glycolysis and immune response were the main risk factors for overall survival (OS) in UM patients. Using univariate Cox regression analysis, 238 candidates related to the prognosis of UM patients were identified (p < 0.05). Using LASSO and multivariate Cox regression analyses, a six-gene signature including ARPC1B, BTBD6, GUSB, KRTCAP2, RHBDD3, and SLC39A4 was constructed. Kaplan-Meier analysis of the UM cohort in the training set showed that patients with higher risk scores had worse OS (HR = 2.61, p < 0.001). The time-dependent ROC (t-ROC) curve showed that the risk score had good predictive efficiency for UM patients in the training set (AUC > 0.9). Besides, t-ROC analysis showed that the predictive ability of risk scores was significantly higher than that of other clinicopathological characteristics. Univariate and multivariate Cox regression analyses showed that risk score was an independent risk factor for OS in UM patients. The prognostic value of risk scores was further verified in two external UM cohorts (GSE22138 and GSE84976). Two-factor survival analysis showed that UM patients with high hypoxia or immune response scores and high risk scores had the worst prognosis. Moreover, a nomogram based on the six-gene signature was established for clinical practice. In addition, risk scores were related to the immune infiltration profiles. Taken together, this study identified a new prognostic six-gene signature related to glycolysis and immune response. This six-gene signature can not only be used for survival prediction and risk stratification but also may be a potential therapeutic target for UM patients.

Liu J ，Lu J ，Li W 《Frontiers in Immunology》

Immune implication of an autophagy-related prognostic signature in uveal melanoma.

Uveal Melanoma (UM) is a rare cancer deriving from melanocytes within the uvea. It has a high rate of metastasis, especially to the liver, and a poor prognosis thereafter. Autophagy, an intracellular programmed digestive process, has been associated with the development and progression of cancers, with controversial pro- and anti-tumour roles. Although previous studies have been conducted on autophagy-related genes (ARGs) in various cancer types, its role in UM requires a deeper understanding for improved diagnosis and development of novel therapeutics. In the present study, Zheng et al. used univariate Cox regression followed by least absolute shrinkage and selection operator (Lasso) regression to identify a robust 9-ARG signature prognostic of survival in a total of 230 patients with UM. The authors used the Cancer Genome Atlas (TCGA) UM cohort as a training cohort (n=80) to identify the signature and validated it in another four independent cohorts of 150 UM patients from the Gene Expression Omnibus (GEO) repository (GSE22138, GSE27831, GSE44295 and GSE84976). This 9-ARG signature was also significantly associated with the enrichment of cancer hallmarks, including angiogenesis, IL6-KJAK-STAT3 signalling, reactive oxygen species pathway and oxidative phosphorylation. More importantly, this signature is associated with immune-related functional pathways and immune cell infiltration. Thus, this 9-ARG signature predicts prognosis and provides deeper insights into the immune mechanisms in UM, with potential implications for future immunotherapy.

Chuah S ，Chew V 《-》

Construction and validation of a pyroptosis-related gene signature associated with the tumor microenvironment in uveal melanoma.

The present study aimed to construct a pyroptosis-related gene signature in uveal melanoma (UM) patients. Patients from The Cancer Genome Atlas (TCGA) served as the training cohort, whereas patients (GSE22138) from Gene Expression Omnibus (GEO) served as the validation cohort. Using the Kaplan-Meier (KM) method, univariate analysis, and least absolute shrinkage and selection operator (LASSO) Cox regression, A five pyroptosis-related gene signature was constructed in the training cohort. Patients were divided into high- and low-risk groups. Survival analysis showed that patients in the high-risk group had a shorter survival time. Risk and survival analysis, time-independent receiver operating characteristic (ROC) curve analysis and principal component analysis (PCA) validated that the prognostic signature had greater predictive value in both cohorts. Multivariate analysis proved that the risk score was an independent prognostic factor. Functional analysis showed that the expressed genes in the high-risk group were most abundant in immunological repose-related and tumor-related signaling pathways. Single-sample gene-set enrichment analysis (ssGSEA) revealed that the different risk groups were associated with the tumor microenvironment. Moreover, the predictive signature could help patients be better matched to immunotherapy and targeted treatments. In conclusion, the pyroptosis-related gene signature associated with the tumor microenvironment maybe a reliable tool for predicting the prognosis of UM patients.

Zhang F ，Deng Y ，Wang D ，Wang S ... -  《Scientific Reports》

Construction and validation of a novel prognostic signature for uveal melanoma based on five metabolism-related genes.

Zhao H ，Chen Y ，Shen P ，Gong L ... -  《-》