Liu Douwaner, Xiong Min, Chen Xiaoting, Wang Xuliren, Sang Yuting, Liu Shiyang, Zhang Liyi, Chi Weiru, Ren Hengyu, Xiu Bingqiu, Zhang Qi, Chi Yayun, Wu Jiong, Xue Jingyan
Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai 200040, China.
Int J Biol Sci. 2025 Jul 25;21(11):4816-4833. doi: 10.7150/ijbs.107763. eCollection 2025.
Breast cancer has the highest incidence among all cancers in women, and the prognosis of breast cancer is strongly linked to the stage of the disease. As one of the components found in liquid biopsy samples, exosomes are membranous vesicles that are actively secreted by living cells. Therefore, the key genes in exosomes may serve as biomarkers for predicting the prognosis of breast cancer patients. In this study, 128 blood samples collected from breast cancer patients at Fudan University Shanghai Cancer Center between June 2018 and March 2019 were subjected to transcriptome sequencing, and the resulting dataset was used as the training dataset. A LASSO regression model was employed for screening prognostic genes. Additionally, 131 patient samples from February 2020 to February 2022 were collected to establish the validation dataset. The corresponding phenotypes and mechanisms of the key genes were confirmed by CCK8 cell proliferation, colony formation, EdU cell proliferation, flow cytometry, transwell cell migration, scratch assay, animal study and RNA-seq assays. Eleven differentially expressed genes tended to increase from the benign stage to the late stage of breast cancer. Five genes were further identified by LASSO regression analysis to establish a prognostic model. The time-dependent receiver operating characteristic (ROC) curves revealed area under the curve (AUC) values of 0.858 for the 1-year follow-up and 0.772 for the 2-year follow-up. The time-dependent ROC curve of the validation dataset indicated an AUC value of 0.840 for the 1-year follow-up. JCAD, a gene closely associated with prognosis, was selected for further investigation. The experimental results demonstrated that JCAD may activate the Wnt/β-catenin pathway by increasing FZD1 expression, thereby promoting the EMT process and breast cancer progression. Exosomal JCAD, as a prognostic marker, plays an important role in the diagnosis and treatment of breast cancer.
乳腺癌在女性所有癌症中的发病率最高,且乳腺癌的预后与疾病分期密切相关。作为液体活检样本中的成分之一,外泌体是活细胞主动分泌的膜性囊泡。因此,外泌体中的关键基因可能作为预测乳腺癌患者预后的生物标志物。在本研究中,收集了2018年6月至2019年3月期间复旦大学附属肿瘤医院乳腺癌患者的128份血液样本进行转录组测序,所得数据集用作训练数据集。采用LASSO回归模型筛选预后基因。此外,收集了2020年2月至2022年2月的131例患者样本以建立验证数据集。通过CCK8细胞增殖、集落形成、EdU细胞增殖、流式细胞术、transwell细胞迁移、划痕试验、动物研究和RNA测序试验证实了关键基因的相应表型和机制。11个差异表达基因在乳腺癌从良性阶段到晚期阶段有升高趋势。通过LASSO回归分析进一步鉴定出5个基因以建立预后模型。时间依赖性受试者工作特征(ROC)曲线显示,1年随访的曲线下面积(AUC)值为0.858,2年随访的AUC值为0.772。验证数据集的时间依赖性ROC曲线显示1年随访的AUC值为0.840。选择与预后密切相关的基因JCAD进行进一步研究。实验结果表明,JCAD可能通过增加FZD1表达激活Wnt/β-连环蛋白通路,从而促进EMT过程和乳腺癌进展。外泌体JCAD作为一种预后标志物,在乳腺癌的诊断和治疗中发挥着重要作用。
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