用AI从常规病理切片预测胰腺癌分子分型,快速低成本且结果可靠。
Inferring Clinically Relevant Molecular Subtypes of Pancreatic Cancer from Routine Histopathology Using Deep Learning
- 基于双尺度深度学习模型,融合细胞形态与组织结构特征
- 内部验证AUC达88.5%,外部独立数据集仍保持84.0%准确率
- 结果可解释,适合临床部署,助力精准治疗决策
胰腺导管腺癌(PDAC)的分子分型(基底样与经典型)具有重要预后和预测价值,但受限于成本、检测周期和组织需求,临床应用受限。本文提出PanSubNet,一种可解释的深度学习框架,直接从标准H&E染色全切片图像(WSIs)预测治疗相关分子亚型。模型基于两个多中心队列共1,055例患者数据(PANCAN,n=846;TCGA,n=209),配对病理与RNA-seq信息构建标签,采用改良的Moffitt 50基因签名结合GATA6表达作为金标准。模型采用双尺度架构,融合细胞级形态与组织级结构,通过注意力机制实现多尺度表征学习与透明特征归因。在PANCAN队列五折交叉验证中,平均AUC为88.5%,敏感性与特异性平衡;在独立的TCGA队列上未微调即达AUC 84.0%,展现良好泛化能力。相比基于RNA-seq的标签,模型在转移性病变中强化了预后分层能力。预测不确定性与中间转录状态相关,非分类噪声。模型预测与已知转录程序、分化标志物及DNA损伤修复信号一致。该方法实现了从常规H&E切片快速、低成本的分子分型,具备临床可部署性与可解释性,支持整合至数字病理流程,推动PDAC精准肿瘤学发展。
原文摘要 · Abstract (English)
Molecular subtyping of PDAC into basal-like and classical has established prognostic and predictive value. However, its use in clinical practice is limited by cost, turnaround time, and tissue requirements, thereby restricting its application in the management of PDAC. We introduce PanSubNet, an interpretable deep learning framework that predicts therapy-relevant molecular subtypes directly from standard H&E-stained WSIs. PanSubNet was developed using data from 1,055 patients across two multi-institutional cohorts (PANCAN, n=846; TCGA, n=209) with paired histology and RNA-seq data. Ground-truth labels were derived using the validated Moffitt 50-gene signature refined by GATA6 expression. The model employs dual-scale architecture that fuses cellular-level morphology with tissue-level architecture, leveraging attention mechanisms for multi-scale representation learning and transparent feature attribution. On internal validation within PANCAN using five-fold cross-validation, PanSubNet achieved mean AUC of 88.5% with balanced sensitivity and specificity. External validation on the independent TCGA cohort without fine-tuning demonstrated robust generalizability (AUC 84.0%). PanSubNet preserved and, in metastatic disease, strengthened prognostic stratification compared to RNA-seq based labels. Prediction uncertainty linked to intermediate transcriptional states, not classification noise. Model predictions are aligned with established transcriptomic programs, differentiation markers, and DNA damage repair signatures. By enabling rapid, cost-effective molecular stratification from routine H&E-stained slides, PanSubNet offers a clinically deployable and interpretable tool for genetic subtyping. We are gathering data from two institutions to validate and assess real-world performance, supporting integration into digital pathology workflows and advancing precision oncology for PDAC.
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