Department of Ophthalmology, Eye Ear Nose and Throat Hospital of Fudan University, Shanghai, 200031, China; Department of Ophthalmology, Shanghai Medical College, Fudan University, Shanghai, 200031, China; NHC Key Laboratory of Myopia (Fudan University), Laboratory of Myopia, Chinese Academy of Medical Sciences, China.
Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Exp Eye Res. 2022 Oct;223:109214. doi: 10.1016/j.exer.2022.109214. Epub 2022 Aug 15.
Uveal melanoma (UM) is the most common primary intraocular tumor with high metastasis and poor prognosis among adults. Hypoxia participates in the metastasis process in various types of cancers. It is reported that the increased expression of hypoxia inducible factor 1 alpha subunit (HIF1A), a hypoxia-related molecule, is associated with worse prognoses of UM patients. Based on the integrated analysis of single-cell sequencing (scRNA-seq) dataset from Gene Expression Omnibus (GEO) and bulk RNA-seq dataset from the Cancer Genome Atlas (TCGA), we found hypoxia was the key feature in UM progression and identified 47 common hypoxia-related differentially expressed genes (DEGs) for the following research. Univariate cox analysis and LASSO-Cox regression analysis were performed to establish a nine-gene prognostic model. According to this model, UM patients could be divided into high- and low-risk groups, with a significant difference in overall survival and progression free survival between the two groups (P < 0.001). The accuracy of the predictive model was also verified on two other independent datasets. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that these hypoxia-related DEGs were enriched in immune and cancer related pathways. The proportion of immune infiltration and the expression of immune biomarkers were different between high- and low-risk UM patients, providing potential targets for UM immunotherapy. Hence, our hypoxia-related nine-gene model could efficiently predict the prognosis and guide personalized therapies for UM patients.
葡萄膜黑色素瘤 (UM) 是成年人中最常见的原发性眼内肿瘤，具有高转移率和预后不良的特点。缺氧参与了各种类型癌症的转移过程。有报道称，缺氧诱导因子 1 ɑ 亚基（HIF1A）这一与缺氧相关的分子表达增加与 UM 患者的预后较差有关。基于基因表达综合数据库（GEO）的单细胞测序（scRNA-seq）数据集和癌症基因组图谱（TCGA）的批量 RNA-seq 数据集的综合分析，我们发现缺氧是 UM 进展的关键特征，并确定了 47 个常见的与缺氧相关的差异表达基因（DEGs）用于进一步研究。单因素 cox 分析和 LASSO-Cox 回归分析用于建立一个由 9 个基因组成的预后模型。根据该模型，UM 患者可分为高风险和低风险组，两组之间的总生存率和无进展生存率存在显著差异（P<0.001）。该预测模型在另外两个独立数据集上的准确性也得到了验证。此外，基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析表明，这些与缺氧相关的 DEGs 富集在免疫和癌症相关通路中。高风险和低风险 UM 患者之间的免疫浸润比例和免疫生物标志物的表达不同，为 UM 免疫治疗提供了潜在的靶点。因此，我们的与缺氧相关的 9 个基因模型可以有效地预测 UM 患者的预后，并指导个体化治疗。
