Abstract

Axillary lymph nodes (ALN) status serves as a crucial prognostic indicator in breast cancer (BC). The aim of this study was to construct a radiogenomic multimodal model, based on machine learning and whole-transcriptome sequencing (WTS), to accurately evaluate the risk of ALN metastasis (ALNM), drug therapeutic response and avoid unnecessary axillary surgery in BC patients. In this study, conducted a retrospective analysis of 1078 BC patients from The Cancer Genome Atlas (TCGA), The Cancer Imaging Archive (TCIA), and Foshan cohort. These patients were divided into the TCIA cohort ( N =103), TCIA validation cohort ( N =51), Duke cohort ( N =138), Foshan cohort ( N =106), and TCGA cohort ( N =680). Radiological features were extracted from BC radiological images and differentially expressed gene expression was calibrated using technology. A support vector machine model was employed to screen radiological and genetic features, and a multimodal model was established based on radiogenomic and clinical pathological features to predict ALNM. The accuracy of the model predictions was assessed using the area under the curve (AUC) and the clinical benefit was measured using decision curve analysis. Risk stratification analysis of BC patients was performed by gene set enrichment analysis, differential comparison of immune checkpoint gene expression, and drug sensitivity testing. For the prediction of ALNM, rad-score was able to significantly differentiate between ALN- and ALN+ patients in both the Duke and Foshan cohorts ( P <0.05). Similarly, the gene-score was able to significantly differentiate between ALN- and ALN+ patients in the TCGA cohort ( P <0.05). The radiogenomic multimodal nomogram demonstrated satisfactory performance in the TCIA cohort (AUC 0.82, 95% CI: 0.74-0.91) and the TCIA validation cohort (AUC 0.77, 95% CI: 0.63-0.91). In the risk sub-stratification analysis, there were significant differences in gene pathway enrichment between high and low-risk groups ( P <0.05). Additionally, different risk groups may exhibit varying treatment responses ( P <0.05). Overall, the radiogenomic multimodal model employs multimodal data, including radiological images, genetic, and clinicopathological typing. The radiogenomic multimodal nomogram can precisely predict ALNM and drug therapeutic response in BC patients.

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