# Advancing Cancer Prognosis with Hierarchical Fusion of Genomic, Proteomic and Pathology Imaging Data from a Systems Biology Perspective

arXiv: https://arxiv.org/abs/2603.13787 · HTML: https://mlsanity.com/paper/2603.13787/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 23 of its 70 references that are in the map.
- First posted on arXiv 14 Mar 2026.

## Builds on (most cited first, 23 of 23)

- [Learning Transferable Visual Models From Natural Language Supervision](https://mlsanity.com/paper/2103.00020/) (2021)
- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Qwen3 Technical Report](https://mlsanity.com/paper/2505.09388/) (2025)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [Self-Normalizing Neural Networks](https://mlsanity.com/paper/1706.02515/) (2017)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Hypergraph Neural Networks](https://mlsanity.com/paper/1809.09401/) (2018)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [DTFD-MIL: Double-Tier Feature Distillation Multiple Instance Learning for Histopathology Whole Slide Image Classification](https://mlsanity.com/paper/2203.12081/) (2022)
- [Quilt-1M: One Million Image-Text Pairs for Histopathology](https://mlsanity.com/paper/2306.11207/) (2023)
- [Gromov-Wasserstein Learning for Graph Matching and Node Embedding](https://mlsanity.com/paper/1901.06003/) (2019)
- [Modeling Dense Multimodal Interactions Between Biological Pathways and Histology for Survival Prediction](https://mlsanity.com/paper/2304.06819/) (2023)
- [Multimodal Optimal Transport-based Co-Attention Transformer with Global Structure Consistency for Survival Prediction](https://mlsanity.com/paper/2306.08330/) (2023)
- [Cross-Modal Translation and Alignment for Survival Analysis](https://mlsanity.com/paper/2309.12855/) (2023)
- [Dynamic Graph Representation with Knowledge-aware Attention for Histopathology Whole Slide Image Analysis](https://mlsanity.com/paper/2403.07719/) (2024)
- [A Multimodal Knowledge-enhanced Whole-slide Pathology Foundation Model](https://mlsanity.com/paper/2407.15362/) (2024)
- [Multimodal Prototyping for cancer survival prediction](https://mlsanity.com/paper/2407.00224/) (2024)
- [Prototypical Information Bottlenecking and Disentangling for Multimodal Cancer Survival Prediction](https://mlsanity.com/paper/2401.01646/) (2024)
- [MoME: Mixture of Multimodal Experts for Cancer Survival Prediction](https://mlsanity.com/paper/2406.09696/) (2024)
- [Robust Multimodal Survival Prediction with the Latent Differentiation Conditional Variational AutoEncoder](https://mlsanity.com/paper/2503.09496/) (2025)
- [ICFNet: Integrated Cross-modal Fusion Network for Survival Prediction](https://mlsanity.com/paper/2501.02778/) (2025)
- [PS3: A Multimodal Transformer Integrating Pathology Reports with Histology Images and Biological Pathways for Cancer Survival Prediction](https://mlsanity.com/paper/2509.20022/) (2025)

## Abstract (arXiv)

To enhance the precision of cancer prognosis, recent research has increasingly focused on multimodal survival methods by integrating genomic data and histology images. However, current approaches overlook the fact that the proteome serves as an intermediate layer bridging genomic alterations and histopathological features while providing complementary biological information essential for survival prediction. This biological reality exposes another architectural limitation: existing integrative analysis studies fuse these heterogeneous data sources in a flat manner that fails to capture their inherent biological hierarchy. To address these limitations, we propose HFGPI, a hierarchical fusion framework that models the biological progression from genes to proteins to histology images from a systems biology perspective. Specifically, we introduce Molecular Tokenizer, a molecular encoding strategy that integrates identity embeddings with expression profiles to construct biologically informed representations for genes and proteins. We then develop Gene-Regulated Protein Fusion (GRPF), which employs graph-aware cross-attention with structure-preserving alignment to explicitly model gene-protein regulatory relationships and generate gene-regulated protein representations. Additionally, we propose Protein-Guided Hypergraph Learning (PGHL), which establishes associations between proteins and image patches, leveraging hypergraph convolution to capture higher-order protein-morphology relationships. The final features are progressively fused across hierarchical layers to achieve precise survival outcome prediction. Extensive experiments on five benchmark datasets demonstrate the superiority of HFGPI over state-of-the-art methods.