PO.TB10.08 · 肿瘤生物学
空间转录组谱分析揭示促纤维增生性小圆细胞肿瘤的异质性
Spatial transcriptomic profiling reveals heterogeneity in desmoplastic small round cell tumor
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
促纤维增生性小圆细胞肿瘤(DSRCT)是一种罕见、侵袭性的软组织肉瘤,由嵌合融合蛋白EWSR1-WT1驱动,该蛋白调控DSRCT肿瘤细胞中的致癌基因表达程序。尽管有此明确的分子驱动因素,DSRCT患者之间的治疗反应和生存结局差异巨大(5年生存率约15%)。我们假设治疗结局的差异反映了肿瘤细胞表型状态、微环境结构和信号网络的异质性。在此,我们使用Xenium 5K空间转录组学在组织微阵列上对来自4例DSRCT患者的7个腹膜和淋巴结转移瘤部位进行了谱分析(1,383,406个细胞)。我们整合了来自15份DSRCT样本(251,087个细胞)的snRNA-seq数据用于细胞类型注释,通过逐患者Leiden聚类(分辨率=0.2)识别患者特异性肿瘤亚型,并通过标志基因评分识别CAF亚型。这揭示了14种患者特异性肿瘤亚型(每位患者3-4种)、三种CAF亚型(apCAFs、myCAFs、iCAFs)、巨噬细胞、T细胞和内皮细胞。
查看英文原文 English abstract
Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive soft tissue sarcoma driven by the chimeric fusion protein EWSR1-WT1 that modulates oncogenic gene expression programs in DSRCT tumor cells. Despite this defined molecular driver, treatment response and survival outcomes vary substantially between DSRCT patients (5-year survival ~ 15%). We hypothesize that treatment outcome variability reflects heterogeneity in tumor cell phenotypic states, microenvironmental architecture, and signaling networks. Here we profiled seven peritoneal and lymph node metastatic tumor sites across four DSRCT patients using Xenium 5K spatial transcriptomics on tissue microarrays (1,383,406 cells). We integrated snRNA-seq data from 15 DSRCT samples (251,087 cells) for cell type annotation, identifying patient-specific tumor subtypes through per-patient Leiden clustering (resolution=0.2) and CAF subtypes through marker gene scoring. This revealed 14 patient-specific tumor subtypes (3-4 per patient), three CAF subtypes (apCAFs, myCAFs, iCAFs), macrophages, T cells, and endothelial cells.
利益披露 Disclosure
E. Sverdlik, None.