用病理切片预测基因表达,可准确判断乳腺癌患者预后。
Evaluation and Prognostic Validation of Deep Regression Models for WSI-Based Gene-Expression Prediction
- 用注意力MIL+病理基础模型直接回归预测基因表达
- 在997例独立乳腺癌数据中验证模型泛化能力,对PAM50等基因集有效
- 预测结果在4172人队列中仍具生存预测价值,适合临床风险分层
基因表达分析在精准肿瘤学中至关重要,但成本高且难以普及。近年计算病理学发展使得从苏木精-伊红染色全幻灯片图像(WSI)直接预测转录组成为可能,但最佳建模策略与临床相关性尚不明确。本研究系统评估了多种深度回归模型在多个回归形式与病理基础模型(PFM)上的表现,并检验预测的转录组信号是否具备预后价值。在四个TCGA数据集中,基于注意力的多实例学习结合PFM特征提取器的直接回归方法表现最优,且无需为不同基因子集分别训练模型。进一步在997例独立乳腺癌患者队列中外部验证,模型对临床相关的基因集(如PAM50)具有稳健泛化能力。在两个包含4,172名患者的代表性乳腺癌队列中,预测基因表达评分在全人群及ER+ & HER2-亚组中均保持显著预后价值。结果表明,基于WSI的基因表达预测能跨队列泛化并恢复生物与临床意义的分子结构,支持其作为可扩展的转录组表型与风险分层工具。
原文摘要 · Abstract (English)
Gene-expression profiling is widely used in research and central to many areas of precision oncology, but remains costly and not universally accessible. Recent advances in computational pathology enable prediction of transcriptomic profiles directly from hematoxylin and eosin (H&E)-stained whole-slide images (WSIs), although optimal modeling strategies and clinical relevance remain unclear. In this study, we systematically evaluate deep regression models for WSI-based gene-expression prediction across multiple regression formulations and pathology foundation models (PFMs), and assess whether the resulting predicted transcriptomic signals retain prognostic utility. Across four TCGA datasets, we find that direct regression using attention-based multiple instance learning together with PFM feature extractors provides a strong and computationally efficient baseline, with no consistent benefit from separately training multiple models on subsets of genes. We then externally validate the selected configuration on an independent cohort of 997 breast cancer patients, demonstrating robust generalization for clinically relevant gene sets such as PAM50. To assess clinical relevance, we further evaluate predicted gene-expression scores in two independent population-representative breast cancer cohorts comprising 4,172 patients with survival endpoints, where predicted scores retain prognostic value in both the full patient cohort and the ER+ & HER2- subgroup. Together, these results demonstrate that WSI-based gene-expression prediction can generalize across independent cohorts and recover biologically and clinically meaningful molecular structure, supporting its potential as a scalable approach for transcriptomic phenotyping and risk stratification.
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