转移是一个复杂的过程，在分子水平上仍然知之甚少。我们分析了 IV 期乳腺癌患者与癌细胞进展、化疗耐药和转移相关的单细胞转录组、基因组和表观基因组变化。收集来自原发肿瘤和远处转移瘤的治疗前和治疗后样本，用于单细胞 RNA 测序和随后的细胞聚类、拷贝数变异 (CNV) 估计、转录组因子估计和伪时间分析。 CNV 分析显示，一小部分治疗前的癌细胞对化疗有抵抗力，并且发生了增殖。包括转移性前体细胞（MPC）在内的新克隆出现在治疗后原发性肿瘤的 CNV 中，与转移性细胞类似。 MPC 表现出表明上皮-间质转化的表达谱。 MPC 与转移性癌细胞的比较还揭示了转录因子和降钙素途径基因表达的动态变化。这些发现证明了单患者临床样本分析对于了解肿瘤耐药性、再生和转移的实用性。© 2024。作者。

Metastasis is a complex process that remains poorly understood at the molecular levels. We profiled single-cell transcriptomic, genomic, and epigenomic changes associated with cancer cell progression, chemotherapy resistance, and metastasis from a Stage IV breast cancer patient. Pretreatment- and posttreatment-specimens from the primary tumor and distant metastases were collected for single-cell RNA sequencing and subsequent cell clustering, copy number variation (CNV) estimation, transcriptomic factor estimation, and pseudotime analyses. CNV analysis revealed that a small population of pretreatment cancer cells resisted chemotherapy and expanded. New clones including Metastatic Precursor Cells (MPCs), emerged in the posttreatment primary tumors in CNV similar to metastatic cells. MPCs exhibited expression profiles indicative of epithelial-mesenchymal transition. Comparison of MPCs with metastatic cancer cells also revealed dynamic changes in transcription factors and calcitonin pathway gene expression. These findings demonstrate the utility of single-patient clinical sample analysis for understanding tumor drug resistance, regrowth, and metastasis.© 2024. The Author(s).