Hu Chuan, Hu Tingting, Wen Jian, Jia Zengrong
Department of Interventional Therapy, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, 310022, China.
School of Medicine, Zhejiang University, Hangzhou, 310009, China.
Mol Med. 2025 Sep 2;31(1):285. doi: 10.1186/s10020-025-01325-z.
Human papillomavirus (HPV) is closely associated with tumor progression and the tumor microenvironment (TME), but its role in breast cancer (BC), which can be affected by HPV, has not been reported.
Ten independent BC cohorts were included to generate two HPV-related gene-based signatures. The CIBERSORT and ESTIMATE algorithms were used to quantify the immune cell fraction and TME scores, and the correlations between HPV-related gene-based signatures and scores were analyzed. The expression patterns and clinical significance of STX11 were determined through bioinformatics analysis, and its effects on modulating tumor-associated macrophages (TAMs) were confirmed by real-time qPCR and Western blotting. The anticancer role of STX11 in macrophages and its underlying mechanisms were analyzed in vitro and in vivo.
Two novel HPV-related gene-based signatures were established that can effectively predict the overall survival and disease-free survival of patients with BC. HPV-related gene-based signatures were significantly associated with the immune score and 19 types of immune cells in BC tissues. STX11 was downregulated in BC and was associated with favorable clinical prognosis, and it was expressed mainly in M1 TAMs. Mechanistically, STX11 promoted the M1 polarization of macrophages, and macrophages overexpressing STX11 can inhibit BC proliferation and migration by regulating the PI3K-AKT pathway. In orthotopic BC models, macrophages overexpressing STX11 significantly suppressed tumor growth.
HPV-related risk signatures were constructed, which showed prognostic predictive ability for patients with BC. STX11 is associated with a favorable prognosis in patients with BC and facilitates M1 polarization, and macrophages overexpressing STX11 can inhibit BC malignancy by regulating the PI3K-AKT pathway, suggesting its role as a potential immunotherapeutic candidate.
人乳头瘤病毒（HPV）与肿瘤进展及肿瘤微环境（TME）密切相关，但其在可受HPV影响的乳腺癌（BC）中的作用尚未见报道。
纳入10个独立的BC队列以生成两个基于HPV相关基因的特征。使用CIBERSORT和ESTIMATE算法量化免疫细胞分数和TME评分，并分析基于HPV相关基因的特征与评分之间的相关性。通过生物信息学分析确定STX11的表达模式和临床意义，并通过实时定量PCR和蛋白质印迹法确认其对调节肿瘤相关巨噬细胞（TAM）的作用。在体外和体内分析了STX11在巨噬细胞中的抗癌作用及其潜在机制。
建立了两个新的基于HPV相关基因的特征，可有效预测BC患者的总生存期和无病生存期。基于HPV相关基因的特征与BC组织中的免疫评分和19种免疫细胞显著相关。STX11在BC中表达下调，与良好的临床预后相关，且主要在M1型TAM中表达。机制上，STX11促进巨噬细胞的M1极化，过表达STX11的巨噬细胞可通过调节PI3K-AKT途径抑制BC的增殖和迁移。在原位BC模型中，过表达STX11的巨噬细胞显著抑制肿瘤生长。
构建了HPV相关风险特征，对BC患者具有预后预测能力。STX11与BC患者的良好预后相关并促进M1极化，过表达STX11的巨噬细胞可通过调节PI3K-AKT途径抑制BC恶性肿瘤，提示其作为潜在免疫治疗候选物的作用。
