Feng Junchao, Hou Yuhan, Liu Chang, Wang Youyou, Chen Weibo, Liu Yulong, Bian Huahui
Department of Nuclear Accident Medical Emergency, The Second Affiliated Hospital of Soochow University Suzhou 215004, Jiangsu, China.
Clinical Diagnosis and Treatment Center of Oncology, The Second Affiliated Hospital of Soochow University Suzhou 215004, Jiangsu, China.
Am J Clin Exp Immunol. 2025 Jun 15;14(3):111-126. doi: 10.62347/XLCY5727. eCollection 2025.
The tumor microenvironment (TME) of breast cancer (BRCA) influences disease progression through dynamic interactions between immunity and stroma, but its key regulatory molecules and prognostic value remain to be elucidated. The aim of this study was to explore the prognostic potential of immunoglobulin λ-like polypeptide 5 (IGLL5) in BRCA and its association with immune infiltration in TME.
1178 BRCA cases were obtained from The Cancer Genome Atlas (TCGA) database. CIBERSORT and ESTIMATE computational methods were used to quantify the composition of tumor-infiltrating immune cells (TICs) and the presence of immune and stromal components. Prognostic indicator closely associated with BRCA was identified by Cox regression analysis and protein-protein interaction (PPI) network construction. Through Gene Set Enrichment Analysis (GSEA) and other means, the correlations between IGLL5 expression and patient survival, immune activities, metabolic pathways, and immune cell types were studied.
Overall survival was significantly prolonged in patients with high IGLL5 expression (HR=0.62, 95% CI 0.45-0.86, =0.013) and positively correlated with immune-activating pathways (complement signaling, interferon response) and anti-tumor TICs (CD8 T cells, M1 macrophages) (r>0.3, <0.001) and negatively correlated with tumor-promoting TICs (M2 macrophages, resting NK cells). The low IGLL5 group was enriched in metabolic pathways (estrogen response, oxidative phosphorylation), suggesting that it may promote immune escape through metabolic reprogramming.
IGLL5 is a novel prognostic marker for BRCA, and its expression level affects patient survival by modulating TME immune infiltration and metabolic reprogramming. This study provides a theoretical basis for IGLL5-directed immunotherapeutic strategies (e.g., combining PD-1 inhibitors), and its mechanism needs to be verified by multicenter clinical cohorts and functional experiments in the future.
乳腺癌（BRCA）的肿瘤微环境（TME）通过免疫与基质之间的动态相互作用影响疾病进展，但其关键调控分子和预后价值仍有待阐明。本研究旨在探讨免疫球蛋白λ样多肽5（IGLL5）在BRCA中的预后潜力及其与TME中免疫浸润的关系。
从癌症基因组图谱（TCGA）数据库中获取1178例BRCA病例。使用CIBERSORT和ESTIMATE计算方法量化肿瘤浸润免疫细胞（TIC）的组成以及免疫和基质成分的存在情况。通过Cox回归分析和蛋白质-蛋白质相互作用（PPI）网络构建，确定与BRCA密切相关的预后指标。通过基因集富集分析（GSEA）等方法，研究IGLL5表达与患者生存、免疫活性、代谢途径和免疫细胞类型之间的相关性。
IGLL5高表达患者的总生存期显著延长（HR=0.62，95%CI 0.45-0.86，P=0.013），且与免疫激活途径（补体信号传导、干扰素反应）和抗肿瘤TIC（CD8 T细胞、M1巨噬细胞）呈正相关（r>0.3，P<0.001），与促肿瘤TIC（M2巨噬细胞、静息NK细胞）呈负相关。低IGLL5组在代谢途径（雌激素反应、氧化磷酸化）中富集，表明其可能通过代谢重编程促进免疫逃逸。
IGLL5是BRCA的一种新型预后标志物，其表达水平通过调节TME免疫浸润和代谢重编程影响患者生存。本研究为以IGLL5为导向的免疫治疗策略（如联合PD-1抑制剂）提供了理论依据，其机制有待未来多中心临床队列和功能实验验证。
