Deep-learning-enabled multi-omics analyses for prediction of future metastasis in cancer
Ma, Q.; Wang, X.; Duan, M.; Su, P.-L.; Li, J.; Krull, J.; Jin, J.; Chen, H.; Sun, Y.; Wu, W.; He, K.; Carpenter, R.; Zhang, C.; Cao, S.; Xu, D.; Wang, G.; Li, L.; Xin, G.; Carbone, D. P.; Li, Z.
Show abstract
Metastasis remains the leading cause of cancer-related mortality, yet predicting future metastasis is a major clinical challenge due to the lack of validated biomarkers and effective assessment methods. Here, we present EmitGCL, a deep-learning framework that accurately predicts future metastasis and its corresponding biomarkers. Based on a comprehensive benchmarking comparison, EmitGCL outperformed other computational tools across six cancer types from seven cohorts of patients with superior sensitivity and specificity. It captured occult metastatic cells in a patient with a lymph node-negative breast cancer, who was declared to have no evidence of disease by conventional imaging methods but was later confirmed to have a metastatic disease. Notably, EmitGCL identified HSP90AA1 and HSP90AB1 as predictable biomarkers for future breast cancer metastasis, which was validated across five independent cohorts of patients (n=420). Furthermore, we demonstrated YY1 transcription factor as a key driver of breast cancer metastasis which was validated through in-silico and CRISPR-based migration assays, suggesting that YY1 is a potential therapeutic target for deterring metastasis.
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