A common cancer in females, breast cancer (BRCA) mortality has been recently reduced; however, the prognosis of BRCA patients remains poor. This study attempted to develop prognostic immune-related long noncoding RNAs (lncRNAs) for BRCA and identify the effects of these lncRNAs on the tumor microenvironment (TME). Gene expression data from The Cancer Genome Atlas (TCGA) database were collected in order to select differentially expressed lncRNAs. Immune-related lncRNAs were downloaded from the ImmLnc database, where 316 immune-related lncRNAs were identified, 12 of which were found to be significantly related to the prognosis of BRCA patients. Multivariate cox regression analysis was then applied to construct prognostic immune-related lncRNAs as the risk model, including C6orf99, LINC00987, SIAH2-AS1, LINC01010, and ELOVL2-AS1. High-risk and low-risk groups were distinguished according to the median of immune-related risk scores. Accordingly, the overall survival (OS) in the high-risk group was observed to be shorter than that in the low-risk group. qRT-PCR analysis demonstrated that lncRNA expression levels in BRCA cell lines were in basic agreement with predictions except for LINC00987. By validating numerous clinical samples, lncRNA C6orf99 was shown to be highly expressed in the advanced stage, while LINC01010 and SIAH2-AS1 decreased in the advanced T-stage and M-stage. Moreover, the expression of LINC0098 was found to be significantly decreased among the groups (>50 years old). Gene set enrichment analysis (GSEA) was applied to analyze the cancer hallmarks and immunological characteristics of the high-risk and low-risk groups. Importantly, the TIMER database demonstrated that this immune-related lncRNA risk model for breast cancer is related to the infiltration of immune cells. In conclusion, the results indicated that five immune-related lncRNAs could be used as a prognostic model and may even accelerate immunotherapy for BRCA patients.

中文翻译：

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五种免疫相关 lncRNA 的鉴定预测乳腺癌的生存和肿瘤微环境特征

作为女性常见的癌症，乳腺癌 (BRCA) 的死亡率最近有所降低；然而，BRCA 患者的预后仍然很差。本研究试图为 BRCA 开发预后免疫相关的长非编码 RNA (lncRNA)，并确定这些 lncRNA 对肿瘤微环境 (TME) 的影响。收集来自癌症基因组图谱 (TCGA) 数据库的基因表达数据以选择差异表达的 lncRNA。从 ImmLnc 数据库下载免疫相关 lncRNA，其中鉴定出 316 个免疫相关 lncRNA，其中 12 个被发现与 BRCA 患者的预后显着相关。然后应用多元cox回归分析构建预后免疫相关lncRNA作为风险模型，包括C6orf99、LINC00987、SIAH2-AS1、LINC01010和ELOVL2-AS1。根据免疫相关风险评分的中位数区分高危组和低危组。因此，观察到高风险组的总生存期 (OS) 比低风险组短。qRT-PCR 分析表明，除了 LINC00987 外，BRCA 细胞系中的 lncRNA 表达水平与预测基本一致。通过对大量临床样本的验证，lncRNA C6orf99 显示在晚期高表达，而 LINC01010 和 SIAH2-AS1 在晚期 T 期和 M 期下降。此外，发现 LINC0098 的表达在各组（> 50 岁）中显着降低。应用基因集富集分析（GSEA）分析高危和低危人群的癌症标志和免疫学特征。重要的，TIMER 数据库证明，这种与免疫相关的 lncRNA 乳腺癌风险模型与免疫细胞的浸润有关。总之，结果表明，五种免疫相关的 lncRNA 可用作预后模型，甚至可能加速 BRCA 患者的免疫治疗。