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

• Published in: Nature communications Vol. 13; no. 1; p. 4250
• Main Authors: Qiu, Lida, Kang, Deyong, Wang, Chuan, Guo, Wenhui, Fu, Fangmeng, Wu, Qingxiang, Xi, Gangqin, He, Jiajia, Zheng, Liqin, Zhang, Qingyuan, Liao, Xiaoxia, Li, Lianhuang, Chen, Jianxin, Tu, Haohua
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.07.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 639/705/794; 692/4028/67/1347; Biomarkers; Breast cancer; Cancer; Computer applications; Extracellular matrix; Gene expression; Graph neural networks; Heterogeneity; Homogenization; Human tissues; Humanities and Social Sciences; Medical prognosis; multidisciplinary; Neural networks; Precision medicine; Prognosis; Regional development; Sampling; Science; Science (multidisciplinary); Spatial heterogeneity; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-31771-w

Biomarkers 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. Cancer prognosis using multiregion sampling is costly and not completely reliable due to the required biomarker homogenisation step. Here, the authors develop an intratumor graph neural network for prognosis in multiregion cancer samples based on in situ biomarkers and gene expression that does not need homogenisation.