The advancement of Spatial Transcriptomics (ST) has facilitated the spatially-aware profiling of gene expressions based on histopathology images. Although ST data offers valuable insights into the micro-environment of tumors, its acquisition cost remains expensive. Therefore, directly predicting the ST expressions from digital pathology images is desired. Current methods usually adopt existing regression backbones along with patch-sampling for this task, which ignores the inherent multi-scale information embedded in the pyramidal data structure of digital pathology images, and wastes the inter-spot visual information crucial for accurate gene expression prediction. To address these limitations, we propose M2OST, a many-to-one regression Transformer that can accommodate the hierarchical structure of the pathology images via a decoupled multi-scale feature extractor. Unlike traditional models that are trained with one-to-one image-label pairs, M2OST uses multiple images from different levels of the digital pathology image to jointly predict the gene expressions in their common corresponding spot. Built upon our many-to-one scheme, M2OST can be easily scaled to fit different numbers of inputs, and its network structure inherently incorporates nearby inter-spot features, enhancing regression performance. We have tested M2OST on three public ST datasets and the experimental results show that M2OST can achieve state-of-the-art performance with fewer parameters and floating-point operations (FLOPs).

Accurate preoperative recurrence prediction for non-small cell lung cancer (NSCLC) is a challenging issue in the medical field. Existing studies primarily conduct image and molecular analyses independently or directly fuse multimodal information through radiomics and genomics, which fail to fully exploit and effectively utilize the highly heterogeneous cross-modal information at different levels and model the complex relationships between modalities, resulting in poor fusion performance and becoming the bottleneck of precise recurrence prediction. To address these limitations, we propose a novel unified framework, the Self-and-Mutual Attention (SAMA) Network, designed to efficiently fuse and utilize macroscopic CT images and microscopic gene data for precise NSCLC recurrence prediction, integrating handcrafted features, deep features, and gene features. Specifically, we design a Self-and-Mutual Attention Module that performs three-stage fusion: the self-enhancement stage enhances modality-specific features; the gene-guided and CT-guided cross-modality fusion stages perform bidirectional cross-guidance on the self-enhanced features, complementing and refining each modality, enhancing heterogeneous feature expression; and the optimized feature aggregation stage ensures the refined interactive features for precise prediction. Extensive experiments on both publicly available datasets from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA) demonstrate that our method achieves state-of-the-art performance and exhibits broad applicability to various cancers.