arXiv:2512.14750q-bio.QMcs.AI2025-12

通过多尺度映射,术前无创预测肾癌分子亚型及预后。

Multiscale Cross-Modal Mapping of Molecular, Pathologic, and Radiologic Phenotypes in Lipid-Deficient Clear Cell Renal CellCarcinoma

  • 构建从分子到病理再到影像的跨模态映射框架。
  • 在1659例患者中实现分子亚型可靠预测,术前风险分层准确。
  • 适合临床医生与研究者用于精准肿瘤评估与治疗决策。

透明细胞肾细胞癌(ccRCC)在多个生物尺度上存在广泛瘤内异质性,导致临床结局差异大,传统TNM分期效果有限,亟需多尺度整合分析框架。脂质缺乏型去分化透明细胞癌(DCCD-ccRCC)由多组学分析定义,即使早期疾病也与不良预后相关。本文建立层级化跨尺度框架,用于术前识别DCCD-ccRCC。最高层实现分子特征向组织学和CT表型的跨模态映射,构建分子→病理→影像的监督桥梁。各模态模型均模拟肿瘤生物学的层级结构:PathoDCCD捕捉从细胞形态、组织架构到中观区域组织的多尺度微观特征;RadioDCCD结合全瘤及其微环境区域的影像组学特征与二维最大截面异质性度量,整合宏观信息。该嵌套模型实现分子亚型预测与临床风险分层。在五个共1,659名患者的队列中,PathoDCCD可靠复现分子亚型,RadioDCCD提供可靠的术前预测。一致预测结果识别出预后最差的患者。此跨尺度范式将分子生物学、计算病理学与定量影像学统一为基于生物机制的非侵入性术前分子表型策略。

原文摘要 · Abstract (English)

Clear cell renal cell carcinoma (ccRCC) exhibits extensive intratumoral heterogeneity on multiple biological scales, contributing to variable clinical outcomes and limiting the effectiveness of conventional TNM staging, which highlights the urgent need for multiscale integrative analytic frameworks. The lipid-deficient de-clear cell differentiated (DCCD) ccRCC subtype, defined by multi-omics analyses, is associated with adverse outcomes even in early-stage disease. Here, we establish a hierarchical cross-scale framework for the preoperative identification of DCCD-ccRCC. At the highest layer, cross-modal mapping transferred molecular signatures to histological and CT phenotypes, establishing a molecular-to-pathology-to-radiology supervisory bridge. Within this framework, each modality-specific model is designed to mirror the inherent hierarchical structure of tumor biology. PathoDCCD captured multi-scale microscopic features, from cellular morphology and tissue architecture to meso-regional organization. RadioDCCD integrated complementary macroscopic information by combining whole-tumor and its habitat-subregions radiomics with a 2D maximal-section heterogeneity metric. These nested models enabled integrated molecular subtype prediction and clinical risk stratification. Across five cohorts totaling 1,659 patients, PathoDCCD reliably recapitulated molecular subtypes, while RadioDCCD provided reliable preoperative prediction. The consistent predictions identified patients with the poorest clinical outcomes. This cross-scale paradigm unifies molecular biology, computational pathology, and quantitative radiology into a biologically grounded strategy for preoperative noninvasive molecular phenotyping of ccRCC.

肾癌多模态影像组学分子分型

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