arXiv:2608.17337cs.CVcs.ET2026-08

从子宫病理图像中挖掘出肿瘤进展的动态状态,突破静态诊断局限。

Learning latent progression states from spatial heterogeneity in uterine histopathology

论文配图:Learning latent progression states from spatial heterogeneity in uterine histopathology
图 1 · 摘自论文原文
  • 基于空间异质性学习形态感知表征,构建肿瘤进展状态图谱。
  • 在10,426张切片上验证,可预测诊断、分子特征和生存期。
  • 无需时间或分子标注,自动发现与临床相关的进展轴线。

肿瘤进展伴随组织结构、形态和微环境的改变,但传统病理学常将这种异质性压缩为静态诊断类别。本文提出专用于子宫的计算病理框架SpaTIE,利用10,426张子宫HE全切片图像,学习形态感知表征,并将空间异质性组织为与进展相关的肿瘤状态。SpaTIE在TCGA-UCEC和TCGA-UCS队列中验证,所学表征形成形态流形,支持诊断、分子及生存预测任务,并定位至关键肿瘤区域。在无时间或分子监督下,该模型从横断面形态推断出肿瘤状态轴线,其空间一致性与临床病理变量及生存结果相关,且不简单复现分期或诊断标签。多组学整合分析揭示这些状态与DNA甲基化、体细胞拷贝数变异、突变、RNA-seq和RPPA谱显著关联,涉及染色质调控、拷贝数相关结构变异、受体酪氨酸激酶信号、细胞黏附、细胞外基质重塑及代谢适应等分子程序。进展引导的虚拟扰动进一步筛选出与形态状态组织耦合的关键分子特征。结果表明,子宫病理图像中蕴含可恢复的进展相关状态信息,SpaTIE为连接空间形态与多组学驱动的肿瘤状态发现提供了新范式。

原文摘要 · Abstract (English)

Tumor progression is accompanied by changes in architecture, morphology and microenvironmental organization, yet progression-associated heterogeneity is usually compressed into static diagnostic categories in histopathology. Here we present SpaTIE, a uterus-specific computational pathology framework that learns morphology-aware representations and organizes spatial histopathological heterogeneity into progression-associated tumor states. SpaTIE was developed using 10,426 uterine hematoxylin and eosin whole-slide images and evaluated in TCGA-UCEC and TCGA-UCS cohorts. The learned representations formed morphology manifolds, supported diagnostic, molecular and survival-related prediction tasks, and localized attention to informative tumor regions. Beyond supervised prediction, SpaTIE inferred tumor-state axes from cross-sectional morphology without temporal or molecular supervision. These morphology-derived states were spatially coherent and showed associations with clinicopathological variables and survival outcomes, while not simply recapitulating staging or diagnostic labels. Integrative multi-omics analyses linked the inferred states to DNA methylation, somatic copy-number variation, mutation, RNA-seq and RPPA profiles, highlighting molecular programs related to chromatin regulation, copy-number-associated structural variation, receptor tyrosine kinase signaling, cell adhesion, extracellular-matrix remodeling and metabolic adaptation. Progression-guided virtual perturbation further prioritized molecular features coupled to the morphology-derived state organization. Together, these findings suggest that uterine histopathology contains recoverable progression-associated tumor-state information and establish SpaTIE as a framework for connecting spatial morphology with multi-omics-informed tumor-state discovery.

计算病理肿瘤进展多组学空间异质性

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