Zhu Chenlei, Xi Tianyi, Yang Guorong, Lu Wen, Wang Sentai, Cao Jiwei
Department of General Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.
Front Oncol. 2025 Jul 21;15:1536278. doi: 10.3389/fonc.2025.1536278. eCollection 2025.
Breast cancer has severe consequences due to late diagnosis and the lack of effective therapies. Currently, potential biomarkers for breast cancer have not been systematically evaluated. Research has shown that JMJD8 is associated with cGAS-STING pathway and plays a role in various tumor microenvironments, but its relationship with breast cancer remains unclear. We investigate the relationship between JMJD8 and the prognosis and immune infiltration microenvironment of breast cancer, exploring its potential as a prognostic biomarker for this type of cancer.
In this study, we utilized data from The Cancer Genome Atlas (TCGA) to assess the association between JMJD8 expression and clinical characteristics in breast cancer (BRCA) patients through the Wilcoxon signed-rank test and logistic regression. Additionally, we employed Kaplan-Meier and Cox regression methods to confirm the impact of JMJD8 expression levels on overall survival. We constructed JMJD8 knockout BRCA cell lines and studied the effects of JMJD8 protein on tumor cell proliferation and anti-tumor immunity at both cellular and animal levels.
Compared to normal tissues, JMJD8 expression levels were significantly elevated in BRCA tissues. High JMJD8 expression was closely associated with advanced pathological stages and was identified as an independent factor negatively impacting overall survival. In both cellular and animal experiments, JMJD8 knockout relieved the inhibition of the cGAS-STING pathway. This resulted in a significant enhancement of the anti-tumor immune response, as it induced dendritic cell (DC) antigen presentation and maturation, ultimately inhibiting the proliferation of BRCA cells. Furthermore, the JMJD8 expression was positively correlated with the infiltration of M2 macrophages in the tumor microenvironment, suggesting that JMJD8 may contribute to the deterioration of the tumor immunosuppressive microenvironment, potentially leading to reduced patient survival.
The elevated expression of JMJD8 in breast cancer tissues is indicative of its involvement in the progression of the disease and its association with immune cell infiltration patterns. Our findings support the hypothesis that JMJD8 could serve as a prognostic biomarker, reflecting the immunosuppressive characteristics of the tumor microenvironment and aiding in the development of targeted therapeutic strategies for breast cancer management.
由于诊断延迟和缺乏有效治疗方法，乳腺癌具有严重后果。目前，尚未对乳腺癌的潜在生物标志物进行系统评估。研究表明，JMJD8与cGAS-STING通路相关，并在各种肿瘤微环境中发挥作用，但其与乳腺癌的关系仍不清楚。我们研究JMJD8与乳腺癌预后及免疫浸润微环境之间的关系，探索其作为这种癌症预后生物标志物的潜力。
在本研究中，我们利用来自癌症基因组图谱（TCGA）的数据，通过Wilcoxon符号秩检验和逻辑回归评估JMJD8表达与乳腺癌（BRCA）患者临床特征之间的关联。此外，我们采用Kaplan-Meier和Cox回归方法来确认JMJD8表达水平对总生存期的影响。我们构建了JMJD8基因敲除的BRCA细胞系，并在细胞和动物水平上研究JMJD8蛋白对肿瘤细胞增殖和抗肿瘤免疫的影响。
与正常组织相比，BRCA组织中JMJD8表达水平显著升高。高JMJD8表达与晚期病理分期密切相关，并被确定为对总生存期有负面影响的独立因素。在细胞和动物实验中，JMJD8基因敲除均缓解了对cGAS-STING通路的抑制。这导致抗肿瘤免疫反应显著增强，因为它诱导了树突状细胞（DC）的抗原呈递和成熟，最终抑制了BRCA细胞的增殖。此外，JMJD8表达与肿瘤微环境中M2巨噬细胞的浸润呈正相关，表明JMJD8可能促成肿瘤免疫抑制微环境的恶化，可能导致患者生存期缩短。
乳腺癌组织中JMJD8表达升高表明其参与疾病进展并与免疫细胞浸润模式相关。我们的研究结果支持这样的假设，即JMJD8可作为一种预后生物标志物，反映肿瘤微环境的免疫抑制特征，并有助于制定乳腺癌治疗的靶向治疗策略。
