Role of gene signature regulation in tumor immune microenvironment on the mechanism of uveal melanoma metastasis

作者全名："Shi, Kai; Tang, Jiatian; Yuan, Lingyan; Zhou, Shengwen; Ran, Wei; Wang, Zhiming"

作者地址："[Shi, Kai; Zhou, Shengwen; Ran, Wei] Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing, Peoples R China; [Shi, Kai; Zhou, Shengwen; Ran, Wei] Chongqing Eye Inst, Chongqing Key Lab Ophthalmol, Chongqing, Peoples R China; [Shi, Kai; Zhou, Shengwen; Ran, Wei] Natl Clin Res Ctr Ocular Dis, Chongqing Branch, Chongqing, Peoples R China; [Tang, Jiatian] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Wuhan, Hubei, Peoples R China; [Yuan, Lingyan] Adv Energy Sci & Technol Guangdong Lab, Huizhou, Guangdong, Peoples R China; [Wang, Zhiming] Gansu Prov Hosp, PET CT Ctr, Lanzhou, Gansu, Peoples R China"

通信作者："Shi, K (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, 1 Youyi Rd, Chongqing, Peoples R China."

来源：CANCER BIOMARKERS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000934805100005

JCR分区：Q3

影响因子：2.2

年份：2023

卷号：36

期号：2

开始页：161

结束页：175

文献类型：Article

关键词：Uveal melanoma; metastasis; tumor immune microenvironment; prognosis; immune related genes

摘要："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."

基金机构：Chongqing Natural Science Foundation [cstc2019jcyj-msxmX0423]; Multidisciplinary Joint Foundation of Gansu Provincial People Hospital [20GSSY2-3]

基金资助正文：This work was supported by the Chongqing Natural Science Foundation (cstc2019jcyj-msxmX0423). This work was also supported by the Multidisciplinary Joint Foundation of Gansu Provincial People Hospital (20GSSY2-3). Immune genes were downloaded from https://www.immport.org/resources.Tumor microenvironment data were obtained from the following website: http://timer.cistrome.org/.