Intratumor graph neural network recovers hidden prognostic value of multi-biomarker spatial heterogeneity

Author:

Qiu Lida,Kang Deyong,Wang Chuan,Guo Wenhui,Fu Fangmeng,Wu QingxiangORCID,Xi Gangqin,He Jiajia,Zheng Liqin,Zhang Qingyuan,Liao Xiaoxia,Li LianhuangORCID,Chen JianxinORCID,Tu Haohua

Abstract

AbstractBiomarkers are indispensable for precision medicine. However, focused single-biomarker development using human tissue has been complicated by sample spatial heterogeneity. To address this challenge, we tested a representation of primary tumor that synergistically integrated multiple in situ biomarkers of extracellular matrix from multiple sampling regions into an intratumor graph neural network. Surprisingly, the differential prognostic value of this computational model over its conventional non-graph counterpart approximated that of combined routine prognostic biomarkers (tumor size, nodal status, histologic grade, molecular subtype, etc.) for 995 breast cancer patients under a retrospective study. This large prognostic value, originated from implicit but interpretable regional interactions among the graphically integrated in situ biomarkers, would otherwise be lost if they were separately developed into single conventional (spatially homogenized) biomarkers. Our study demonstrates an alternative route to cancer prognosis by taping the regional interactions among existing biomarkers rather than developing novel biomarkers.

Funder

U.S. Department of Health and Human Services

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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