Zhong Xiaoxiao, Han Jiaxuan, Li Huan, Shen Xiangyu, Yu Bowen, Chen Ting, Li Haobing, Li Jun, Pang Jin, Qian Liyuan, Wu Wei, Tong Xiaoliang, Ding Boni
Department of Breast and Thyroid Surgery, Third Xiangya Hospital, Central South University, Changsha, 410000, Hunan, China.
Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, 410000, Hunan, China.
Mamm Genome. 2025 May 24. doi: 10.1007/s00335-025-10137-9.
The tumor microenvironment (TME) and aberrant glycosylation have been suggested to play key roles in cancer. This study integrated differentially expressed genes (DEGs) and weighted gene coexpression network analysis (WGCNA) to identify tumor microenvironment-related genes and construct a TME-risk prognostic signature (TMERS) through LASSO Cox regression. After batch effect removal, 44 TME-prognosis-related genes (TMEPGs) were identified and classified into three molecular subtypes via K-means clustering. The finalized 22-gene TMERS model demonstrated robust prognostic predictive capacity in GEO datasets. The results revealed distinct immune profiles and prognostic stratifications among genetic subtypes and risk groups, confirming that the TMERS is an independent prognostic indicator for breast cancer (BRCA). Glycosyltransferase genes (GTs) have potential therapeutic relevance through immune regulation, with TMEPG member killer cell lectin like receptor B1 (KLRB1) significantly correlated with BRCA prognosis. Cellular experiments demonstrated that KLRB1 overexpression suppressed BRCA cell proliferation and migration. This work establishes a novel prognostic model for BRCA while highlighting KLRB1 as a potential biomarker, providing new insights into TME-targeted therapeutic strategies.
肿瘤微环境（TME）和异常糖基化被认为在癌症中起关键作用。本研究整合差异表达基因（DEG）和加权基因共表达网络分析（WGCNA）来识别肿瘤微环境相关基因，并通过LASSO Cox回归构建TME风险预后特征（TMERS）。去除批次效应后，鉴定出44个TME预后相关基因（TMEPG），并通过K均值聚类将其分为三种分子亚型。最终确定的22基因TMERS模型在GEO数据集中显示出强大的预后预测能力。结果揭示了基因亚型和风险组之间不同的免疫特征和预后分层，证实TMERS是乳腺癌（BRCA）的独立预后指标。糖基转移酶基因（GT）通过免疫调节具有潜在的治疗相关性，TMEPG成员杀伤细胞凝集素样受体B1（KLRB1）与BRCA预后显著相关。细胞实验表明，KLRB1过表达抑制BRCA细胞增殖和迁移。这项工作建立了一种新的BRCA预后模型，同时强调KLRB1作为潜在生物标志物，为TME靶向治疗策略提供了新见解。
