Cheng Yaqi, Liu Chengxiu, Liu Yurun, Su Yaru, Wang Shoubi, Jin Lin, Wan Qi, Liu Ying, Li Chaoyang, Sang Xuan, Yang Liu, Liu Chang, Wang Xiaoran, Wang Zhichong
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Department of Ophthalmology, Affiliated Hospital of Qingdao University Medical College, Qingdao, China.
Front Oncol. 2020 Oct 27;10:577072. doi: 10.3389/fonc.2020.577072. eCollection 2020.
Cutaneous melanoma is the most life-threatening skin malignant tumor due to its increasing metastasis and mortality rate. The abnormal competitive endogenous RNA network promotes the development of tumors and becomes biomarkers for the prognosis of various tumors. At the same time, the tumor immune microenvironment (TIME) is of great significance for tumor outcome and prognosis. From the perspective of TIME and ceRNA network, this study aims to explain the prognostic factors of cutaneous melanoma systematically and find novel and powerful biomarkers for target therapies. We obtained the transcriptome data of cutaneous melanoma from The Cancer Genome Atlas (TCGA) database, 3 survival-related mRNAs co-expression modules and 2 survival-related lncRNAs co-expression modules were identified through weighted gene co-expression network analysis (WCGNA), and 144 prognostic miRNAs were screened out by univariate Cox proportional hazard regression. Cox regression model and Kaplan-Meier survival analysis were employed to identify 4 hub prognostic mRNAs, and the prognostic ceRNA network consisting of 7 lncRNAs, 1 miRNA and 4 mRNAs was established. After analyzing the composition and proportion of total immune cells in cutaneous melanoma microenvironment through CIBERSORT algorithm, it is found through correlation analysis that lncRNA-TUG1 in the ceRNA network was closely related to the TIME. In this study, we first established cutaneous melanoma's TIME-related ceRNA network by WGCNA. Cutaneous melanoma prognostic markers have been identified from multiple levels, which has important guiding significance for clinical diagnosis, treatment, and further scientific research on cutaneous melanoma.
皮肤黑色素瘤因其不断增加的转移率和死亡率,成为最具生命威胁的皮肤恶性肿瘤。异常的竞争性内源RNA网络促进肿瘤发展,并成为各种肿瘤预后的生物标志物。同时,肿瘤免疫微环境(TIME)对肿瘤的结局和预后具有重要意义。本研究从TIME和ceRNA网络的角度出发,旨在系统阐释皮肤黑色素瘤的预后因素,并寻找新的、有效的生物标志物用于靶向治疗。我们从癌症基因组图谱(TCGA)数据库获取了皮肤黑色素瘤的转录组数据,通过加权基因共表达网络分析(WCGNA)鉴定出3个与生存相关的mRNA共表达模块和2个与生存相关的lncRNA共表达模块,并通过单变量Cox比例风险回归筛选出144个预后miRNA。采用Cox回归模型和Kaplan-Meier生存分析鉴定出4个核心预后mRNA,并建立了由7个lncRNA、1个miRNA和4个mRNA组成的预后ceRNA网络。通过CIBERSORT算法分析皮肤黑色素瘤微环境中总免疫细胞的组成和比例后,经相关性分析发现ceRNA网络中的lncRNA-TUG1与TIME密切相关。在本研究中,我们首先通过WGCNA建立了皮肤黑色素瘤的TIME相关ceRNA网络。已从多个层面鉴定出皮肤黑色素瘤的预后标志物,这对皮肤黑色素瘤的临床诊断、治疗及进一步的科学研究具有重要指导意义。