Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Department of Cardiology, The 7th People's Hospital of Zhengzhou, Zhengzhou 450006, China.
Comput Math Methods Med. 2021 Feb 27;2021:6676692. doi: 10.1155/2021/6676692. eCollection 2021.
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.
女性常见癌症乳腺癌(BRCA)的死亡率最近有所降低;然而,BRCA 患者的预后仍然较差。本研究试图为 BRCA 开发预后免疫相关长非编码 RNA(lncRNA),并确定这些 lncRNA 对肿瘤微环境(TME)的影响。从癌症基因组图谱(TCGA)数据库中收集基因表达数据,以选择差异表达的 lncRNA。从 ImmLnc 数据库中下载免疫相关 lncRNA,其中鉴定出 316 个免疫相关 lncRNA,其中 12 个与 BRCA 患者的预后显著相关。然后应用多变量 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将高风险组和低风险组区分开来。相应地,高风险组的总生存期(OS)观察到比低风险组短。qRT-PCR 分析表明,BRCA 细胞系中 lncRNA 表达水平与预测基本一致,除 LINC00987 外。通过验证大量临床样本,发现 lncRNA C6orf99 在晚期表达水平较高,而 LINC01010 和 SIAH2-AS1 在晚期 T 期和 M 期表达水平降低。此外,LINC0098 的表达在>50 岁的组中明显降低。基因集富集分析(GSEA)用于分析高风险和低风险组的癌症特征和免疫特征。重要的是,TIMER 数据库表明,这种乳腺癌免疫相关 lncRNA 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 lncRNA 可用作预后模型,甚至可能加速 BRCA 患者的免疫治疗。