Zhao Dongyi, Zhu Shida, Bai Xue, Li Xuelu, Zhao Zuowei
Department of Breast Surgery, The Second Hospital of Dalian Medical University, Dalian, 116023, China.
Discov Oncol. 2025 May 19;16(1):814. doi: 10.1007/s12672-025-02586-0.
Pure mucinous breast cancer is an uncommon form of cancer characterized by a low metastatic rate and a generally favorable prognosis. However, some patients may experience lymph node metastasis, leading to a worse prognosis. Currently, there is no reliable in vitro model available to effectively address the heterogeneity of pure mucinous breast cancer.
We obtained surgical tumor samples from a 64-year-old Chinese female patient diagnosed with pure mucinous breast cancer to establish patient-derived organoids. Using these organoids, we performed histological staining, drug testing and single-cell RNA-Seq analysis.
We accomplished the establishment of a patient-derived mucinous breast cancer organoid model from a Chinese female. Hematoxylin and eosin staining, along with immunohistochemistry, revealed histology and protein expression (ER, PR, HER2 and Ki-67) at early passages similar to the original breast cancer tissue. Single-cell RNA sequencing at passage 7 identified 17 cell clusters, which were assigned to three cell types based on marker genes. This showed that most ER-positive luminal cells had been replaced by ER-negative basal-like cells at passage 7. We tested drug sensitivity to five antitumor drugs at passage 5. The organoids showed the highest sensitivity to Epirubicin and the lowest sensitivity to Carboplatin.
This is the first reported case of a mucinous breast cancer organoid. Our experimental results indicate that this model exhibits similar characteristics to the original tissue at early passages. Organoids at early passages could be a promising tool for clinical drug screening and further scientific research.
纯黏液性乳腺癌是一种罕见的癌症形式，其特点是转移率低且总体预后良好。然而，一些患者可能会发生淋巴结转移，导致预后较差。目前，尚无可靠的体外模型可有效解决纯黏液性乳腺癌的异质性问题。
我们从一名64岁诊断为纯黏液性乳腺癌的中国女性患者身上获取手术肿瘤样本，以建立患者来源的类器官。利用这些类器官，我们进行了组织学染色、药物测试和单细胞RNA测序分析。
我们成功建立了一名中国女性患者来源的黏液性乳腺癌类器官模型。苏木精和伊红染色以及免疫组化显示，早期传代时的组织学和蛋白表达（雌激素受体、孕激素受体、人表皮生长因子受体2和Ki-67）与原始乳腺癌组织相似。第7代的单细胞RNA测序鉴定出17个细胞簇，根据标记基因将其分为三种细胞类型。这表明在第7代时，大多数雌激素受体阳性的管腔细胞已被雌激素受体阴性的基底样细胞取代。我们在第5代测试了对五种抗肿瘤药物的药敏性。类器官对表柔比星的敏感性最高，对卡铂的敏感性最低。
这是首例报道的黏液性乳腺癌类器官病例。我们的实验结果表明，该模型在早期传代时表现出与原始组织相似的特征。早期传代的类器官可能是临床药物筛选和进一步科学研究的有前途的工具。
