Wang Wanpeng, Wang Sha
Eye Center of Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Ophthalmology, Changsha, China.
Front Oncol. 2022 Aug 16;12:918230. doi: 10.3389/fonc.2022.918230. eCollection 2022.
Uveal melanoma (UM) is an aggressive malignancy with a poor prognosis and no available effective treatment. Therefore, exploring a potential prognostic marker for UM could provide new possibilities for early detection, recurrence, and treatment.
In this study, we used "ConsensusClusterPlus" to classify patients with UM into subgroups, screened for significant differences in immune prognostic factors between subgroups, selected three genes using LASSO (Least absolute shrinkage and selection operator) regression to construct a risk model, and performed tumor immune cell infiltration analysis on the risk model. infiltration analysis, and then verified the heterogeneous role of the 3 core genes in other cancers by pan-cancer analysis and validate its expression by RT-qPCR in normal and tumor cells.
We consistently categorized 80 UM patients into two subgroups after the immunogenetic set, where the UM1 subgroup had a better prognosis than the UM2 subgroup, and used 3 immune-related genes AZGP1, SLCO5A1, and CTF1 to derive risk scores as independent prognostic markers and predictors of UM clinicopathological features. We found significant differences in overall survival (OS) between low- and high-risk groups, and prognostic models were negatively correlated with B cell and myeloid dendritic cell and positively correlated with CD8+ T cell AZGP1 and CTF1 were significantly upregulated in UM cells compared with normal UM cells.
Immunogens are significantly associated with the prognosis of UM, and further classification based on genetic characteristics may help to develop immunotherapeutic strategies and provide new approaches to develop customized treatment strategies for patients.
葡萄膜黑色素瘤（UM）是一种侵袭性恶性肿瘤，预后较差且尚无有效的治疗方法。因此，探索UM潜在的预后标志物可为早期检测、复发及治疗提供新的可能性。
在本研究中，我们使用“ConsensusClusterPlus”将UM患者分为亚组，筛选亚组间免疫预后因素的显著差异，使用LASSO（最小绝对收缩和选择算子）回归选择三个基因构建风险模型，并对该风险模型进行肿瘤免疫细胞浸润分析，然后通过泛癌分析验证这3个核心基因在其他癌症中的异质性作用，并通过RT-qPCR在正常细胞和肿瘤细胞中验证其表达。
在免疫遗传数据集后，我们将80例UM患者一致分为两个亚组，其中UM1亚组的预后优于UM2亚组，并使用3个免疫相关基因AZGP1、SLCO5A1和CTF1得出风险评分，作为UM临床病理特征的独立预后标志物和预测指标。我们发现低风险组和高风险组之间的总生存期（OS）存在显著差异，预后模型与B细胞和髓样树突状细胞呈负相关，与CD8+T细胞呈正相关。与正常UM细胞相比，UM细胞中AZGP1和CTF1显著上调。
免疫原与UM的预后显著相关，基于遗传特征的进一步分类可能有助于制定免疫治疗策略，并为为患者制定个性化治疗策略提供新方法。
