Chen Gang, Cao Jianqiao, Zhao Huishan, Cong Yizi, Qiao Guangdong
Department of Breast Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, China.
Reproductive Medicine Centre, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, China.
Cent Eur J Immunol. 2022;47(2):139-150. doi: 10.5114/ceji.2022.118081. Epub 2022 Jul 15.
Breast cancer (BC) is the most common cancer in women worldwide and has a high mortality rate. The fact that the tumor microenvironment affects clinical outcomes of all types of cancers underlines the involvement of various immune-related genes (IRGs). Therefore, this study aimed to establish an IRGs-based signature for the prognosis of BC patients.
In this study, 12 immune cell infiltrating degrees in 1,102 BC cases from The Cancer Genome Atlas (TCGA) database were assessed, and RNA-sequencing (RNA-seq) data of these samples were analyzed by single-sample gene set enrichment analysis (ssGSEA). Based on the results, high, low, and middle immune infiltrating clusters were constructed. A total of 138 overlapped differentially expressed genes (DEGs) were identified in the high and low infiltrating clusters, as well as in normal and BC samples. Univariate Cox regression and LASSO analyses were also performed. Furthermore, GSEA suggested some highly enriched pathways in the different immune infiltrating clusters, leading to a better understanding of potential mechanisms of immune infiltration in BC.
Finally, 19 immune-related genes were identified that could be utilized as a potential prognostic biomarker for BC. Kaplan-Meier plot and ROC curve, univariate as well as multivariate Cox analyses were carried out, which suggested that the 19-IRG-based signature is a significant prognosis factor independent of clinical features. Based on the analysis of protein-protein interactions (PPI), the three hub genes were identified.
These results provide a new method to predict the prognosis and survival of BC based on the three genes' features.
乳腺癌（BC）是全球女性中最常见的癌症，死亡率很高。肿瘤微环境影响所有类型癌症的临床结果，这一事实凸显了各种免疫相关基因（IRG）的参与。因此，本研究旨在建立基于IRG的特征来预测BC患者的预后。
在本研究中，评估了来自癌症基因组图谱（TCGA）数据库的1102例BC病例中的12种免疫细胞浸润程度，并通过单样本基因集富集分析（ssGSEA）对这些样本的RNA测序（RNA-seq）数据进行了分析。基于结果，构建了高、低和中等免疫浸润簇。在高浸润簇和低浸润簇以及正常样本和BC样本中总共鉴定出138个重叠的差异表达基因（DEG）。还进行了单变量Cox回归和LASSO分析。此外，基因集富集分析（GSEA）表明在不同免疫浸润簇中有一些高度富集的通路，有助于更好地理解BC中免疫浸润的潜在机制。
最终，鉴定出19个免疫相关基因，可作为BC潜在的预后生物标志物。进行了Kaplan-Meier曲线和ROC曲线分析，以及单变量和多变量Cox分析，结果表明基于19个IRG的特征是一个独立于临床特征的显著预后因素。基于蛋白质-蛋白质相互作用（PPI）分析，鉴定出三个枢纽基因。
这些结果提供了一种基于这三个基因特征预测BC预后和生存的新方法。
