Affiliations: [a] The First Affiliated Hospital of Chongqing Medical University, Chongqing, China | [b] Chongqing Key Lab of Ophthalmology, Chongqing Eye Institute, Chongqing, China | [c] Chongqing Branch of National Clinical Research Center for Ocular Diseases, Chongqing, China | [d] Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China | [e] Advanced Energy Science and Technology Guangdong Laboratory, Huizhou, Guangdong, China | [f] PET/CT Center, Gansu Provincial Hospital, Lanzhou, Gansu, China
Correspondence:
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Corresponding author: Kai Shi, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, China. Tel.: +86 15608354792; E-mail: [email protected].
Abstract: BACKGROUND: Uveal melanoma (UM) is a rare but deadly cancer. The main cause of death from UM is liver metastasis. Though the metastasis mechanism remains unclear, it is closely related to the immune microenvironment and gene expression. OBJECTIVE: This study aimed to identify the prognostic genes in primary and metastatic UM and their relationship with the immune microenvironment. METHODS: Primary and metastatic UM data from the GEO database included GSE22138 and GSE44295 datasets. Kaplan-Meier analysis, Cox regression models, and ROC analysis were applied to screen genes in GSE22138. TIMER2.0 was employed to analyze the immune microenvironment from gene expression. Prognostic immune gene correlation was tested by Spearman. The results were validated in the independent dataset of cohort GSE44295. RESULTS: Metastasis and primary differential gene analysis showed 107 significantly different genes associated with prognosis, and 11 of them were immune-related. ROC analysis demonstrated that our signature was predictive for UM prognosis (AUC > 0.8). Neutrophil and myeloid dendritic cells were closely associated with metastasis with scores that significantly divided patients into high-risk and low-risk groups (log-rank p< 0.05). Of these 11 genes, FABP5 and SHC4 were significantly associated with neutrophils in metastatic tumors, while ROBO1 expression was significantly correlated with myeloid dendritic cells in the primary tumors. CONCLUSIONS: The present study constructed an 11-gene signature and established a model for risk stratification and prediction of overall survival in metastatic UM. Since FABP5 and SHC4 are related to neutrophil infiltration in metastatic UM, FABP5 and neutrophil regulation might be crucial in metastatic UM.
