State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Department of Ophthalmology, The People's Hospital of Leshan, Leshan, Sichuan, China.
Cancer Biomark. 2020;27(3):343-356. doi: 10.3233/CBM-190825.
Uveal melanoma (UM) is the most common primary intraocular tumor in adults, which has a high mortality rate and worse prognosis. Therefore, early potential molecular detection and prognostic evaluation seem more important for early diagnosis and treatment.
Gene expression data were obtained from The Cancer Genome Atlas-Uveal melanomas database. Survival genes were identified by univariate analysis and were regarded to be associated with the overall survival of UM patients. Then, pathway enrichment analysis of these survival genes was performed. Robust likelihood-based survival model and multivariate survival analysis were conducted to identify more reliable genes and the prognostic signature for UM survival prediction. Two internal datasets and another two UM datasets from Gene Expression Omnibus (GEO) were used for the validation of prognostic signature.
Firstly, 2,010 survival genes were screened by univariate survival analysis. GO and KEGG analysis revealed that these genes were mainly involved in pathways such as mRNA processing, RNA splicing, spliceosome and ubiquitin mediated proteolysis. Secondly, a six-gene signature was identified by Robust likelihood-based survival model approach. The gene expression of the six genes can successfully divide UM samples into high- and low-risk groups and have strong survival prediction ability. What's more, the expression of six genes was compared in 80 healthy adipose tissue samples obtained from GTEx (Genotype-Tissue Expression) database and further validated in internal datasets and GEO datasets, which also can predict UM patient survival.
The six genes (SH2D3A, TMEM201, LZTS1, CREG1, NIPA1 and HIST1H4E) model might play a vital role in prognosis of UM, which should be helpful for further insight into the treatment of uveal melanoma.
葡萄膜黑色素瘤(UM)是成年人中最常见的原发性眼内肿瘤,其死亡率高,预后差。因此,早期潜在的分子检测和预后评估对于早期诊断和治疗似乎更为重要。
从癌症基因组图谱-葡萄膜黑色素瘤数据库中获取基因表达数据。通过单因素分析确定生存基因,并认为这些基因与 UM 患者的总生存率相关。然后,对这些生存基因进行通路富集分析。进行稳健似然生存模型和多变量生存分析,以确定更可靠的基因和 UM 生存预测的预后特征。两个内部数据集和另外两个来自基因表达综合(GEO)的 UM 数据集用于验证预后特征。
首先,通过单因素生存分析筛选出 2010 个生存基因。GO 和 KEGG 分析表明,这些基因主要参与 mRNA 加工、RNA 剪接、剪接体和泛素介导的蛋白水解等途径。其次,通过稳健似然生存模型方法确定了一个由六个基因组成的特征。六个基因的表达可以成功地将 UM 样本分为高风险和低风险组,具有很强的生存预测能力。更重要的是,在 GTEx(基因型-组织表达)数据库中获得的 80 个健康脂肪组织样本中比较了六个基因的表达,并在内部数据集和 GEO 数据集中进一步验证,这也可以预测 UM 患者的生存。
六个基因(SH2D3A、TMEM201、LZTS1、CREG1、NIPA1 和 HIST1H4E)模型可能在 UM 的预后中起重要作用,这有助于进一步深入了解葡萄膜黑色素瘤的治疗。