Department of Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, China.
Front Immunol. 2021 Apr 23;12:664845. doi: 10.3389/fimmu.2021.664845. eCollection 2021.
Female breast cancer (BCa) is the most commonly occurring cancer worldwide. The tumor microenvironment (TME) plays an essential role in tumor invasion, angiogenesis, unlimited proliferation, and even immune escape, but we know little about the TME of BCa. In this study, we aimed to find a TME-related biomarker for BCa, especially for invasive breast carcinoma (BRCA), that could predict prognosis and immunotherapy efficacy. Based on RNA-seq transcriptome data and the clinical characteristics of 1222 samples (113 normal and 1109 tumor samples) from The Cancer Genome Atlas (TCGA) database, we used the ESTIMATE algorithm to calculate the ImmuneScore and StromalScore and then identified differentially expressed genes (DEGs) between the high and low ImmuneScore groups and the high and low StromalScore groups. Thereafter, a protein-protein interaction (PPI) network analysis and univariate Cox regression analyses of overall survival were used to identify potential key genes. Five candidate genes were identified, comprising CD2, CCL19, CD52, CD3E, and ITK. Thereafter, we focused on CD2, analyzing CD2 expression and its association with survival. CD2 expression was associated with tumor size (T stage) to some extent, but not with overall TNM stage, lymph node status (N stage), or distant metastasis (M stage). High CD2 expression was associated with longer survival. METABRIC data were used to validate the survival result (n = 276). Gene set enrichment analysis (GSEA) showed that the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were significantly associated with high CD2 expression were mainly immune-related pathways. Furthermore, CD2 expression was correlated with 16 types of tumor-infiltrating immune cells (TICs). Hence, CD2 might be a novel biomarker in terms of molecular typing, and it may serve as a complementary approach to TNM staging to improve clinical outcome prediction for BCa patients.
女性乳腺癌（BCa）是全球最常见的癌症。肿瘤微环境（TME）在肿瘤侵袭、血管生成、无限增殖甚至免疫逃逸中起着至关重要的作用，但我们对 BCa 的 TME 知之甚少。在这项研究中，我们旨在寻找一种与 TME 相关的 BCa 生物标志物，特别是用于预测预后和免疫治疗效果的浸润性乳腺癌（BRCA）。我们基于 RNA-seq 转录组数据和来自癌症基因组图谱（TCGA）数据库的 1222 个样本（113 个正常和 1109 个肿瘤样本）的临床特征，使用 ESTIMATE 算法计算免疫评分和基质评分，然后鉴定出高和低免疫评分组以及高和低基质评分组之间的差异表达基因（DEGs）。之后，进行蛋白质-蛋白质相互作用（PPI）网络分析和总生存的单变量 Cox 回归分析，以鉴定潜在的关键基因。确定了五个候选基因，包括 CD2、CCL19、CD52、CD3E 和 ITK。此后，我们专注于 CD2，分析 CD2 表达及其与生存的关联。CD2 的表达与肿瘤大小（T 分期）有一定的相关性，但与整体 TNM 分期、淋巴结状态（N 分期）或远处转移（M 分期）无关。高 CD2 表达与更长的生存时间相关。我们使用 METABRIC 数据验证了生存结果（n=276）。基因集富集分析（GSEA）表明，与高 CD2 表达显著相关的京都基因与基因组百科全书（KEGG）途径主要与免疫相关途径有关。此外，CD2 的表达与 16 种肿瘤浸润免疫细胞（TICs）相关。因此，CD2 可能是一种新的分子分型生物标志物，它可以作为 TNM 分期的补充方法，提高 BCa 患者的临床结果预测能力。
