Yu Xiaojie, Zhang Hao, Liu Jing, Hou Changran, Zhang Haojie, Yang Zhenlin
Department of Thyroid Surgery, Binzhou Medical University Hospital, Binzhou, Shandong, 256603, P.R. China.
Department of Blood Transfusion, Binzhou Medical University Hospital, Binzhou, Shandong, 256603, P.R. China.
Comb Chem High Throughput Screen. 2025;28(6):973-987. doi: 10.2174/0113862073293963240409040110.
The tumor microenvironment (TME) exerts a significant influence on the development, invasion, metastasis, and drug resistance of breast cancer. Therefore, this study sought to investigate potential prognostic factors and markers indicative of TME remodeling in breast cancer, utilizing data from the TCGA database.
In this study, transcriptome RNA-seq data from 1222 breast cancer samples were processed using CIBERSORT and ESTIMATE algorithms. We conducted a differential gene expression analysis utilizing COX regression analysis and constructed protein-protein interaction (PPI) networks for enhanced visualization. Through univariate COX analysis and cross-analysis within PPI networks, the Interleukin-7 receptor (IL-7R) emerged as a potential predictor. Subsequently, we performed a comprehensive investigation encompassing single-gene survival analysis, clinical correlation assessment, and GSEA enrichment analysis targeting IL-7R as a core gene associated with prognosis. We examined the expression of IL-7R in human breast cancer and normal breast tissue through clinical studies and cytology experiments, followed by an indepth analysis of the relationship between IL-7R and breast cancer.
The survival analysis revealed that breast cancer patients with elevated IL-7R expression experienced prolonged survival compared to those with lower IL-7R levels. Results obtained from the Wilcoxon rank-sum test, along with clinical and cellular experiments, indicated higher IL-7R expression in tumor samples compared to normal samples. Correlation tests conducted between IL-7R expression and clinicopathological stage characteristics highlighted statistically significant associations between IL-7R expression and the T and M stages. Additionally, cell classification analysis of tumor-infiltrating immune cells (TIC) proportion showed that activated CD4+ T cells and CD8 T cells of memory B cells were positively correlated with IL-7R expression. These findings further underscored the impact of IL-7R levels on the tumor microenvironment (TME).
IL-7R emerges as a potential prognostic indicator for breast cancer patients, particularly in sustaining the immunoactive status of the tumor microenvironment (TME) and contributing to immune reconstitution. These findings offer novel insights into breast cancer treatment strategies.
肿瘤微环境(TME)对乳腺癌的发生、侵袭、转移及耐药性具有重大影响。因此,本研究利用TCGA数据库的数据,旨在探究乳腺癌中提示TME重塑的潜在预后因素和标志物。
在本研究中,使用CIBERSORT和ESTIMATE算法处理来自1222例乳腺癌样本的转录组RNA测序数据。我们利用COX回归分析进行差异基因表达分析,并构建蛋白质-蛋白质相互作用(PPI)网络以增强可视化。通过单变量COX分析和PPI网络内的交叉分析,白细胞介素-7受体(IL-7R)成为一个潜在的预测因子。随后,我们以IL-7R作为与预后相关的核心基因,进行了包括单基因生存分析、临床相关性评估和GSEA富集分析在内的全面研究。我们通过临床研究和细胞学实验检测了IL-7R在人乳腺癌和正常乳腺组织中的表达,随后深入分析了IL-7R与乳腺癌之间的关系。
生存分析显示,与IL-7R水平较低的乳腺癌患者相比,IL-7R表达升高的患者生存期延长。Wilcoxon秩和检验结果以及临床和细胞实验表明,肿瘤样本中的IL-7R表达高于正常样本。IL-7R表达与临床病理分期特征之间的相关性测试突出了IL-7R表达与T和M分期之间具有统计学意义的关联。此外,肿瘤浸润免疫细胞(TIC)比例的细胞分类分析表明,记忆B细胞的活化CD4 + T细胞和CD8 T细胞与IL-7R表达呈正相关。这些发现进一步强调了IL-7R水平对肿瘤微环境(TME)的影响。
IL-7R成为乳腺癌患者的潜在预后指标,特别是在维持肿瘤微环境(TME)的免疫活性状态和促进免疫重建方面。这些发现为乳腺癌治疗策略提供了新的见解。