本研究旨在系统地建立一个综合性的肿瘤微环境（TME）相关预后基因和靶向miRNA网络，以应用于乳腺癌患者。基于大规模筛选TME相关预后基因（760个基因）进行预后模型的建立。主要TME预后基因从构建数据库中挑选，并在测试数据库中验证。深入探究TME潜在预后基因与乳腺癌患者预后之间的内部关系。生成与TME预后基因相关的miRNA，并研究每个主要TME成员在乳腺癌细胞系中的功能。与兄弟对照组相比，乳腺癌患者表现出55个差异表达的TME预后基因，其中31个被认为是保护性基因，而其余24个基因被认为是风险基因。根据LASSO Cox分析的lambda值，15 个潜在的TME预后基因为：ENPEP、CCDC102B、FEZ1、NOS2、SCG2、RPLP2、RELB、RGS3、EMP1、PDLIM4、EPHA3、PCDH9、VIM、GFI1和IRF1。其中，CCDC102B存在着显著的线性内部关系，但其他TME预后基因与乳腺癌患者预后之间存在非线性关系。借助siRNA技术，我们沉默了每个TME预后基因的表达。其中7个TME预后基因（NOS2、SCG2、RGS3、EMP1、PDLIM4、PCDH9和GFI1）参与增强乳腺癌细胞的增殖、破坏细胞凋亡、促进细胞侵袭或迁移。另外6个TME预后基因（CCDC102B、RPLP2、RELB、EPHA3、VIM和IRF1）有利于维持细胞侵袭或迁移。只有两个TME预后基因（ENPEP和FEZ1）有利于细胞增殖和凋亡过程。本整合研究提出了一个创新的与TME相关的遗传功能网络，用于乳腺癌患者的应用。测量这些TME预后基因与疾病之间的外部关系，同时也研究了内部分子机制。版权所有©2023年Xiao、Li、Cui、Yin和Zhang。

The aim of this study was to systematically establish a comprehensive tumour microenvironment (TME)-relevant prognostic gene and target miRNA network for breast cancer patients.Based on a large-scale screening of TME-relevant prognostic genes (760 genes) for breast cancer patients, the prognostic model was established. The primary TME prognostic genes were selected from the constructing database and verified in the testing database. The internal relationships between the potential TME prognostic genes and the prognosis of breast cancer patients were explored in depth. The associated miRNAs for the TME prognostic genes were generated, and the functions of each primary TME member were investigated in the breast cancer cell line.Compared with sibling controls, breast cancer patients showed 55 differentially expressed TME prognostic genes, of which 31 were considered as protective genes, while the remaining 24 genes were considered as risk genes. According to the lambda values of the LASSO Cox analysis, the 15 potential TME prognostic genes were as follows: ENPEP, CCDC102B, FEZ1, NOS2, SCG2, RPLP2, RELB, RGS3, EMP1, PDLIM4, EPHA3, PCDH9, VIM, GFI1, and IRF1. Among these, there was a remarkable linear internal relationship for CCDC102B but non-linear relationships for others with breast cancer patient prognosis. Using the siRNA technique, we silenced the expression of each TME prognostic gene. Seven of the 15 TME prognostic genes (NOS2, SCG2, RGS3, EMP1, PDLIM4, PCDH9, and GFI1) were involved in enhancing cell proliferation, destroying cell apoptosis, promoting cell invasion, or migration in breast cancer. Six of them (CCDC102B, RPLP2, RELB, EPHA3, VIM, and IRF1) were favourable for maintaining cell invasion or migration. Only two of them (ENPEP and FEZ1) were favourable for the processes of cell proliferation and apoptosis.This integrated study hypothesised an innovative TME-associated genetic functional network for breast cancer patients. The external relationships between these TME prognostic genes and the disease were measured. Meanwhile, the internal molecular mechanisms were also investigated.Copyright © 2023 Xiao, Li, Cui, Yin and Zhang.