Liu Hongsen, Chen Mengting, Hong Bo, Liang Ruijin, Fan Lijie, Qian Yun
Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China.
Department of Clinical Laboratory, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou, 310000, China.
Med Oncol. 2025 Jul 21;42(8):355. doi: 10.1007/s12032-025-02943-7.
Breast cancer is among the most prevalent malignancies, with lymph node metastasis strongly linked to worse prognostic outcomes. Despite this, the mechanisms underlying the formation of an immunosuppressive microenvironment that drives lymph node metastasis remain poorly understood. By profiling 118,127 cells from eight patients with breast cancer alongside their metastatic axillary lymph nodes through single-cell sequencing and spatial transcriptomics, this study uncovered the activation of the pentose phosphate pathway during the metastatic process. The expression level of G6PD in breast cancer tumor tissues was significantly higher than that in adjacent tissues. Furthermore, high G6PD expression was associated with poorer prognosis. G6PD was more highly expressed in metastatic lymph nodes, which exhibited an immunosuppressive microenvironment induced by CD4 Treg cells, and the expression of G6PD was positively correlated with immune cell infiltration by Treg cells. Clinical evaluation further demonstrated a significant correlation among G6PD expression, lymph node metastasis, and malignancy. Additionally, clinical drug response data revealed that patients resistant to chemotherapy also had higher G6PD expression. These findings establish G6PD as a molecular marker for predicting the risk of lymph node metastasis and prognosis in breast cancer. This study discovered elevated expression of G6PD in breast cancer, as well as the formation of an immunosuppressive microenvironment mediated by Treg cells in breast cancer lymph node metastatic tissues, emphasizing the critical role of G6PD in promoting lymph node metastasis by driving Treg cell infiltration.
乳腺癌是最常见的恶性肿瘤之一，淋巴结转移与较差的预后结果密切相关。尽管如此，驱动淋巴结转移的免疫抑制微环境形成的潜在机制仍知之甚少。通过单细胞测序和空间转录组学对8例乳腺癌患者及其转移性腋窝淋巴结中的118,127个细胞进行分析，本研究发现了转移过程中磷酸戊糖途径的激活。乳腺癌肿瘤组织中G6PD的表达水平显著高于相邻组织。此外，高G6PD表达与较差的预后相关。G6PD在转移性淋巴结中表达更高，这些淋巴结表现出由CD4 Treg细胞诱导的免疫抑制微环境，并且G6PD的表达与Treg细胞的免疫细胞浸润呈正相关。临床评估进一步证明了G6PD表达、淋巴结转移和恶性程度之间存在显著相关性。此外，临床药物反应数据显示，对化疗耐药的患者G6PD表达也更高。这些发现确立了G6PD作为预测乳腺癌淋巴结转移风险和预后的分子标志物。本研究发现乳腺癌中G6PD表达升高，以及乳腺癌淋巴结转移组织中由Treg细胞介导的免疫抑制微环境的形成，强调了G6PD通过驱动Treg细胞浸润促进淋巴结转移的关键作用。
