Integrating single-cell transcriptomics with Artificial Intelligence reveals pan-cancer biomarkers of brain metastasis

Abstract

Brain metastasis (BrM) is a serious complication of advanced cancers and remains difficult to predict before clinical symptoms appear. To investigate shared transcriptional features of BrM across tumour types, we integrated single-cell RNA sequencing (scRNA-seq) data from malignant epithelial cells derived from six carcinoma types, including lung, breast, colorectal, renal, ovarian, and melanoma. We applied ScaiVision, a supervised representation learning method, to classify tumour samples based on BrM status. The models achieved high predictive accuracy (area under the ROC curve > 0.90) across all six cancer types. This analysis identified a consistent multi-cancer gene expression signature associated with BrM, defined at single-cell resolution. To evaluate the clinical relevance of this signature, we assessed its presence in tumour-educated platelets (TEPs) from blood samples of patients with and without BrM. The signature was detectable in platelet RNA and distinguished patients with BrM from those without, indicating that features of the BrM-associated expression program are reflected in blood-derived material. These findings demonstrate that a transcriptional signature of brain metastasis can be identified across multiple tumour types using scRNA-seq and neural network-based analysis. The detectability of this signature in TEPs supports its relevance in a non-invasive context and provides a basis for further investigation into its utility for BrM risk assessment.