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胶原蛋白紊乱结构特征与结肠癌的临床、分子、遗传因素及生存结果相关。

Collagen disorder architecture features are associated with clinical, molecular, genetic factors and survival outcomes in colon cancer.

作者信息

Nag Reetoja, Chen Chuheng, Mejbel Haider, Li Haojia, Aqeel Aya, Fu Pingfu, Corredor Germán, Khalighi Sirvan, Pathak Tilak, Mokhtari Mojgan, Reid Michelle Dian, Krasinskas Alyssa M, Pandav Krunal, Willis Joseph E, Madabhushi Anant

机构信息

Emory University, Atlanta, GA, USA.

Case Western Reserve University, Cleveland, OH, USA.

出版信息

NPJ Precis Oncol. 2025 Aug 28;9(1):304. doi: 10.1038/s41698-025-01098-y.


DOI:10.1038/s41698-025-01098-y
PMID:40877439
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12394695/
Abstract

We developed a computational pathology pipeline to extract and analyze collagen disorder architecture (CoDA) features from whole slide images (WSIs) of 2,212 colon cancer (CC) patients across multiple institutions. CoDA features-capturing collagen fragmentation, bundling, anisotropy, density, and rigidity, were evaluated for associations with clinical variables (overall stage, T/N/M stage), molecular classifications (Consensus Molecular Subtypes [CMS1-4]), and genetic mutations (KRAS, BRAF, NRAS) using the Mann-Whitney U test with Bonferroni correction. These analyses revealed significant differences in CoDA feature distributions across multiple subgroups, suggesting that collagen architecture varies meaningfully with tumor stage, molecular subtype, and mutation status.To assess how well CoDA features could distinguish between these subgroups, we implemented a Random Forest classification framework. High mean AUC values (≥0.7) across several variables indicated strong discriminatory performance of CoDA features in separating clinically and biologically distinct groups.For survival analysis, LASSO-Cox models were trained on the PLCO dataset to generate CoDA-based risk scores for overall survival (OS) and disease-free survival (DFS), which were used to stratify patients into high- and low-risk groups in a combined validation dataset (TCGA, UH, and Emory). Kaplan-Meier curves demonstrated significant survival differences across clinical stages, CMS subtypes, and KRAS mutation status. Multivariable Cox proportional hazards models further confirmed the independent prognostic value of CoDA features after adjusting for clinical, molecular, and genetic covariates. These findings highlight that CoDA features are significantly associated with key clinical and molecular characteristics, can distinguish relevant patient subgroups, and offer independent prognostic information, underscoring their potential utility in characterizing the tumor microenvironment and informing risk stratification in CC.

摘要

我们开发了一种计算病理学流程,用于从多个机构的2212例结肠癌(CC)患者的全切片图像(WSI)中提取和分析胶原紊乱结构(CoDA)特征。使用带有Bonferroni校正的Mann-Whitney U检验,评估了捕捉胶原碎片、束状结构、各向异性、密度和硬度的CoDA特征与临床变量(总体分期、T/N/M分期)、分子分类(共识分子亚型[CMS1-4])和基因突变(KRAS、BRAF、NRAS)之间的关联。这些分析揭示了多个亚组之间CoDA特征分布的显著差异,表明胶原结构随肿瘤分期、分子亚型和突变状态有显著变化。为了评估CoDA特征在区分这些亚组方面的效果,我们实施了一个随机森林分类框架。几个变量的高平均AUC值(≥0.7)表明CoDA特征在区分临床和生物学上不同的组方面具有很强的鉴别性能。对于生存分析,在PLCO数据集上训练LASSO-Cox模型,以生成基于CoDA的总生存(OS)和无病生存(DFS)风险评分,这些评分用于在一个联合验证数据集(TCGA、UH和埃默里大学)中将患者分层为高风险和低风险组。Kaplan-Meier曲线显示了不同临床分期、CMS亚型和KRAS突变状态之间的显著生存差异。多变量Cox比例风险模型在调整临床、分子和遗传协变量后进一步证实了CoDA特征的独立预后价值。这些发现突出表明,CoDA特征与关键的临床和分子特征显著相关,可以区分相关的患者亚组,并提供独立的预后信息,强调了它们在表征肿瘤微环境和为CC中的风险分层提供信息方面的潜在效用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46f3/12394695/6ee8fac18636/41698_2025_1098_Fig11_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46f3/12394695/b808624e814e/41698_2025_1098_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46f3/12394695/eb5c87859a2d/41698_2025_1098_Fig10_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46f3/12394695/b02488124ba7/41698_2025_1098_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46f3/12394695/d25bd4a2008a/41698_2025_1098_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46f3/12394695/6aaee030eaf8/41698_2025_1098_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46f3/12394695/9b6da48222f4/41698_2025_1098_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46f3/12394695/4708f793acbb/41698_2025_1098_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46f3/12394695/3dd74ab9ed93/41698_2025_1098_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46f3/12394695/3d6be7c923ee/41698_2025_1098_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46f3/12394695/b808624e814e/41698_2025_1098_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46f3/12394695/eb5c87859a2d/41698_2025_1098_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46f3/12394695/6ee8fac18636/41698_2025_1098_Fig11_HTML.jpg

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Oncology. 2023-3-23

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