Li Chen, Wang Xiaolong, Chen Tong, Li Wenhao, Yang Qifeng
Department of Breast Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
Department of Pathology Tissue Bank, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
Int J Gen Med. 2022 May 27;15:5253-5272. doi: 10.2147/IJGM.S366335. eCollection 2022.
In recent years, breast cancer (BC) has been a primary cause of mortality in women. However, the underlying mechanisms remain to be elucidated. Accumulating evidence has supported the hypothesis that long noncoding RNAs (lncRNAs) play central roles in the progression of cancer. We aimed to construct an immune-related lncRNA panel to predict the prognosis of patients with BC and evaluate the immune features.
The expression profiles of patients with BC were obtained from The Cancer Genome Atlas (TCGA) database to screen the differentially expressed lncRNAs (DELs). Pearson's correlation analysis was employed to filter the DELs related to the immune-associated genes. Univariate Cox regression, the LASSO algorithm, and multivariate Cox regression analyses were conducted to establish the model. Functional enrichment analyses and biological experiments were performed to explore the immune activity of the lncRNA panel.
A four-immune-related lncRNA panel (IRLP) composed of AC022196.1, ARHGAP26-AS1, DPYD-AS1 and PURPL was established in TCGA training cohort. The prognostic accuracy of the predictive model was confirmed in TCGA internal validation cohort, TCGA entire cohort and Qilu external validation cohort. Bioinformatics analyses indicated that the IRLP had a close relationship with tumour infiltrating immune cells and immunomodulatory biomarkers. The biological functions of the four immune-related lncRNAs in BC were first investigated in vitro and in vivo. PURPL was indicated to play a central role in the regulation of macrophage recruitment and polarization via CCL2.
Our study identified IRLP as a reliable prognostic indicator with great potential for clinical application in personalized immunotherapy.
近年来，乳腺癌（BC）一直是女性死亡的主要原因。然而，其潜在机制仍有待阐明。越来越多的证据支持了长链非编码RNA（lncRNAs）在癌症进展中起核心作用的假说。我们旨在构建一个免疫相关lncRNApanel来预测BC患者的预后并评估免疫特征。
从癌症基因组图谱（TCGA）数据库中获取BC患者的表达谱，以筛选差异表达的lncRNAs（DELs）。采用Pearson相关性分析来筛选与免疫相关基因相关的DELs。进行单变量Cox回归、LASSO算法和多变量Cox回归分析以建立模型。进行功能富集分析和生物学实验以探索lncRNApanel的免疫活性。
在TCGA训练队列中建立了一个由AC022196.1、ARHGAP26-AS1、DPYD-AS1和PURPL组成的四免疫相关lncRNApanel（IRLP）。在TCGA内部验证队列、TCGA整个队列和齐鲁外部验证队列中证实了预测模型的预后准确性。生物信息学分析表明，IRLP与肿瘤浸润免疫细胞和免疫调节生物标志物密切相关。首次在体外和体内研究了四种免疫相关lncRNAs在BC中的生物学功能。结果表明，PURPL通过CCL2在巨噬细胞募集和极化的调节中起核心作用。
我们的研究确定IRLP是一种可靠的预后指标，在个性化免疫治疗中具有巨大的临床应用潜力。
