arXiv:2511.15067cs.LGcs.AI2025-11

用AI分析病理切片,精准预测肠癌预后并发现新靶点。

Deep Pathomic Learning Defines Prognostic Subtypes and Molecular Drivers in Colorectal Cancer

  • 基于全幻灯片图像的深度学习模型,自动提取病理特征。
  • 风险分层效果优于传统分期,高危组与代谢异常和免疫抑制相关。
  • 发现线粒体蛋白MRPL37是关键预后基因,适合临床决策辅助。

结直肠癌(CRC)异质性强,传统TNM分期难以满足个体化治疗需求。本文开发并验证了一种新型多实例学习模型TDAM-CRC,利用组织病理全幻灯片图像实现精准预后预测,并揭示其分子机制。模型在TCGA发现队列(n=581)训练,在独立外部队列(n=1031)验证,表现显著优于传统分期及多个前沿模型。多组学分析显示高危亚型与代谢重编程及免疫抑制性肿瘤微环境密切相关。通过互作网络分析,鉴定并验证了线粒体核糖体蛋白L37(MRPL37)为连接深度病理特征与临床预后的关键枢纽基因。高表达的MRPL37由启动子低甲基化驱动,是独立的有利预后标志物。最终构建包含TDAM-CRC风险评分与临床因素的列线图,提供可解释的临床决策工具。该AI病理模型实现了更优的肠癌风险分层,揭示新分子靶点,推动个体化诊疗。

原文摘要 · Abstract (English)

Precise prognostic stratification of colorectal cancer (CRC) remains a major clinical challenge due to its high heterogeneity. The conventional TNM staging system is inadequate for personalized medicine. We aimed to develop and validate a novel multiple instance learning model TDAM-CRC using histopathological whole-slide images for accurate prognostic prediction and to uncover its underlying molecular mechanisms. We trained the model on the TCGA discovery cohort (n=581), validated it in an independent external cohort (n=1031), and further we integrated multi-omics data to improve model interpretability and identify novel prognostic biomarkers. The results demonstrated that the TDAM-CRC achieved robust risk stratification in both cohorts. Its predictive performance significantly outperformed the conventional clinical staging system and multiple state-of-the-art models. The TDAM-CRC risk score was confirmed as an independent prognostic factor in multivariable analysis. Multi-omics analysis revealed that the high-risk subtype is closely associated with metabolic reprogramming and an immunosuppressive tumor microenvironment. Through interaction network analysis, we identified and validated Mitochondrial Ribosomal Protein L37 (MRPL37) as a key hub gene linking deep pathomic features to clinical prognosis. We found that high expression of MRPL37, driven by promoter hypomethylation, serves as an independent biomarker of favorable prognosis. Finally, we constructed a nomogram incorporating the TDAM-CRC risk score and clinical factors to provide a precise and interpretable clinical decision-making tool for CRC patients. Our AI-driven pathological model TDAM-CRC provides a robust tool for improved CRC risk stratification, reveals new molecular targets, and facilitates personalized clinical decision-making.

癌症预后AI病理多组学列线图

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