The Second Clinical Medical College, Jinan University, Shenzhen, China.
Biomedical Research Institute, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China.
Front Immunol. 2022 Jun 14;13:922315. doi: 10.3389/fimmu.2022.922315. eCollection 2022.
Ferroptosis is a newly iron-dependent mode of programmed cell death that is involved in a variety of malignancies. But no research has shown a link between ferroptosis-related long non-coding RNAs (FRLs) and uveal melanoma (UM). We aimed to develop a predictive model for UM and explore its potential function in relation to immune cell infiltration.
Identification of FRLs was performed using the Cancer Genome Atlas (TCGA) and FerrDb databases. To develop a prognostic FRLs signature, univariate Cox regression and least absolute shrinkage and selection operator (LASSO) were used in training cohort. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curve analyses were used to assess the reliability of the risk model. The immunological functions of FRLs signature were determined using gene set enrichment analysis (GSEA). Immunological cell infiltration and immune treatment were studied using the ESTIMATE, CIBERSORT, and ssGSEA algorithms. Finally, assays were carried out to confirm the biological roles of FRLs with known primer sequences (LINC00963, PPP1R14B.AS1, and ZNF667.AS1).
A five-genes novel FRLs signature was identified. The mean risk score generated by this signature was used to create two risk groups. The high-risk score UM patients had a lower overall survival rate. The area under the curve (AUC) of ROC and K-M analysis further validated the strong prediction capacity of the prognostic signature. Immune cells such as memory CD8 T cells, M1 macrophages, monocytes, and B cells showed a substantial difference between the two groups. GSEA enrichment results showed that the FRLs signature was linked to certain immune pathways. Moreover, UM patients with high-risk scores were highly susceptible to several chemotherapy drugs, such as cisplatin, imatinib, bortezomib, and pazopanib. Finally, the experimental validation confirmed that knockdown of three identified lncRNA (LINC00963, PPP1R14B.AS1, and ZNF667.AS1) suppressed the invasive ability of tumor cells .
The five-FRLs (AC104129.1, AC136475.3, LINC00963, PPP1R14B.AS1, and ZNF667.AS1) signature has effects on clinical survival prediction and selection of immunotherapies for UM patients.
铁死亡是一种新发现的铁依赖性程序性细胞死亡方式，与多种恶性肿瘤有关。但是，目前还没有研究表明铁死亡相关长非编码 RNA（FRLs）与葡萄膜黑色素瘤（UM）之间存在关联。我们旨在建立一个 UM 的预测模型，并探索其与免疫细胞浸润相关的潜在功能。
使用癌症基因组图谱（TCGA）和 FerrDb 数据库鉴定 FRLs。使用单因素 Cox 回归和最小绝对值收缩和选择算子（LASSO）在训练队列中开发预后 FRLs 特征。使用 Kaplan-Meier（K-M）和受试者工作特征（ROC）曲线分析评估风险模型的可靠性。使用基因集富集分析（GSEA）确定 FRLs 特征的免疫学功能。使用 ESTIMATE、CIBERSORT 和 ssGSEA 算法研究免疫细胞浸润和免疫治疗。最后，使用已知引物序列（LINC00963、PPP1R14B.AS1 和 ZNF667.AS1）的实验验证来确认 FRLs 的生物学作用。
确定了一个由五个新的 FRLs 组成的特征。使用该特征生成的平均风险评分用于创建两个风险组。高风险评分的 UM 患者总生存率较低。ROC 和 K-M 分析的曲线下面积（AUC）进一步验证了预后特征的强大预测能力。记忆 CD8 T 细胞、M1 巨噬细胞、单核细胞和 B 细胞等免疫细胞在两组之间存在显著差异。GSEA 富集结果表明，FRLs 特征与某些免疫途径有关。此外，高风险评分的 UM 患者对几种化疗药物（如顺铂、伊马替尼、硼替佐米和帕唑帕尼）高度敏感。最后，实验验证证实，敲低三个鉴定出的 lncRNA（LINC00963、PPP1R14B.AS1 和 ZNF667.AS1）抑制了肿瘤细胞的侵袭能力。
五个 FRLs（AC104129.1、AC136475.3、LINC00963、PPP1R14B.AS1 和 ZNF667.AS1）特征对 UM 患者的临床生存预测和免疫治疗选择有影响。
