Metastasis is the leading cause of cancer-related mortality, yet most predictive models rely on shallow architectures and neglect patient-specific regulatory mechanisms. Here, we integrate classical machine learning and deep learning to predict metastatic potential across multiple cancer types. Gene expression profiles from the Cancer Cell Line Encyclopedia were combined with a transcription factor-target prior from DoRothEA, focusing on nine metastasis-associated regulators. After selecting differential genes using the Kruskal-Wallis test, ElasticNet, Random Forest, and XGBoost models were trained for benchmarking. Personalized gene regulatory networks were then constructed using PANDA and LIONESS and analyzed through a graph attention neural network (GATv2) to learn topological and expression-based representations. While XGBoost achieved the highest AUROC (0.7051), the GNN captured non-linear regulatory dependencies at the patient level. These results demonstrate that combining traditional machine learning with graph-based deep learning enables a scalable and interpretable framework for metastasis risk prediction in precision oncology.
Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major com
Recurrence and metastasis have been regarded as two of the greatest obstacles for curing cancer. Cancer stem cell (CSC) have been found. They contribute to cancer development with the distinct feature of recurrence and resistance to the popular treatments such as drugs and chemotherapy. In addition, recent discoveries suggest that the epithelial mesenchymal transition (EMT) is an essential process in normal embryogenesis and tissue repair, which is a required step in cancer metastasis. Although there are many indications showing the connections between metastasis and stem cell, researches often studied them separately or at most bi-laterally, not in an integrated way. In this study, we aim at exploring the global mechanisms and interrelationship among cancer, development and metastasis which are currently poorly understood. To start, we constructed a core gene regulatory network motif which contain specific genes and microRNAs of CSC, EMT and cancer. We uncovered seven distinct states emerged from the underlying landscape. They are identified as Normal, Premalignant, Cancer, stem cell (SC), cancer stem cell (CSC), Lesion and Hyperlasia state. Given the biological definition of each
Bone metastasis analysis is a significant challenge in pathology and plays a critical role in determining patient quality of life and treatment strategies. The microenvironment and specific tissue structures are essential for pathologists to predict the primary bone cancer origins and primary bone cancer subtyping. By digitizing bone tissue sections into whole slide images (WSIs) and leveraging deep learning to model slide embeddings, this analysis can be enhanced. However, tumor metastasis involves complex multivariate interactions with diverse bone tissue structures, which traditional WSI analysis methods such as multiple instance learning (MIL) fail to capture. Moreover, graph neural networks (GNNs), limited to modeling pairwise relationships, are hard to represent high-order biological associations. To address these challenges, we propose a dynamic hypergraph neural network (DyHG) that overcomes the edge construction limitations of traditional graph representations by connecting multiple nodes via hyperedges. A low-rank strategy is used to reduce the complexity of parameters in learning hypergraph structures, while a Gumbel-Softmax-based sampling strategy optimizes the patch di
Esophageal cancer is one of the most common types of cancer worldwide and ranks sixth in cancer-related mortality. Accurate computer-assisted diagnosis of cancer progression can help physicians effectively customize personalized treatment plans. Currently, CT-based cancer diagnosis methods have received much attention for their comprehensive ability to examine patients' conditions. However, multi-modal based methods may likely introduce information redundancy, leading to underperformance. In addition, efficient and effective interactions between multi-modal representations need to be further explored, lacking insightful exploration of prognostic correlation in multi-modality features. In this work, we introduce a multi-modal heterogeneous graph-based conditional feature-guided diffusion model for lymph node metastasis diagnosis based on CT images as well as clinical measurements and radiomics data. To explore the intricate relationships between multi-modal features, we construct a heterogeneous graph. Following this, a conditional feature-guided diffusion approach is applied to eliminate information redundancy. Moreover, we propose a masked relational representation learning strate
While machine learning has advanced in medicine, its widespread use in clinical applications, especially in predicting breast cancer metastasis, is still limited. We have been dedicated to constructing a DFNN model to predict breast cancer metastasis n years in advance. However, the challenge lies in efficiently identifying optimal hyperparameter values through grid search, given the constraints of time and resources. Issues such as the infinite possibilities for continuous hyperparameters like l1 and l2, as well as the time-consuming and costly process, further complicate the task. To address these challenges, we developed Single Hyperparameter Grid Search (SHGS) strategy, serving as a preselection method before grid search. Our experiments with SHGS applied to DFNN models for breast cancer metastasis prediction focus on analyzing eight target hyperparameters: epochs, batch size, dropout, L1, L2, learning rate, decay, and momentum. We created three figures, each depicting the experiment results obtained from three LSM-I-10-Plus-year datasets. These figures illustrate the relationship between model performance and the target hyperparameter values. For each hyperparameter, we analyz
Multimodal Machine Learning offers a holistic view of a patient's status, integrating structured and unstructured data from electronic health records (EHR). We propose a framework to predict metastasis risk one month prior to diagnosis, using six months of clinical history from EHR data. Data from four cancer cohorts collected at Karolinska University Hospital (Stockholm, Sweden) were analyzed: breast (n = 743), colon (n = 387), lung (n = 870), and prostate (n = 1890). The dataset included demographics, comorbidities, laboratory results, medications, and clinical text. We compared traditional and deep learning classifiers across single modalities and multimodal combinations, using various fusion strategies and a Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) 2a design, with an 80-20 development-validation split to ensure a rigorous, repeatable evaluation. Performance was evaluated using AUROC, AUPRC, F1 score, sensitivity, and specificity. We then employed a multimodal adaptation of SHAP to analyze the classifiers' reasoning. Intermediate fusion achieved the highest F1 scores on breast (0.845), colon (0.786), and prostate ca
Accurate preoperative assessment of lymph node (LN) metastasis in rectal cancer guides treatment decisions, yet conventional MRI evaluation based on morphological criteria shows limited diagnostic performance. While some artificial intelligence models have been developed, they often operate as black boxes, lacking the interpretability needed for clinical trust. Moreover, these models typically evaluate nodes in isolation, overlooking the patient-level context. To address these limitations, we introduce LRMR, an LLM-Driven Relational Multi-node Ranking framework. This approach reframes the diagnostic task from a direct classification problem into a structured reasoning and ranking process. The LRMR framework operates in two stages. First, a multimodal large language model (LLM) analyzes a composite montage image of all LNs from a patient, generating a structured report that details ten distinct radiological features. Second, a text-based LLM performs pairwise comparisons of these reports between different patients, establishing a relative risk ranking based on the severity and number of adverse features. We evaluated our method on a retrospective cohort of 117 rectal cancer patients
Colorectal cancer liver metastasis (CRLM) exhibits high postoperative recurrence and pronounced prognostic heterogeneity, challenging individualized management. Existing prognostic approaches often rely on static representations from a single postoperative snapshot, and fail to jointly capture tumor spatial distribution, longitudinal disease dynamics, and multimodal clinical information, limiting predictive accuracy. We propose DyPro, a deep learning framework that infers postoperative latent trajectories via residual dynamic evolution. Starting from an initial patient representation, DyPro generates a 12-step sequence of trajectory snapshots through autoregressive residual updates and integrates them to predict recurrence and survival outcomes. On the MSKCC CRLM dataset, DyPro achieves strong discrimination under repeated stratified 5-fold cross-validation, reaching a C-index of 0.755 for OS and 0.714 for DFS, with OS AUC@1y of 0.920 and OS IBS of 0.143. DyPro provides quantitative risk cues to support adjuvant therapy planning and follow-up scheduling.
Advances in optical microscopy scanning have significantly contributed to computational pathology (CPath) by converting traditional histopathological slides into whole slide images (WSIs). This development enables comprehensive digital reviews by pathologists and accelerates AI-driven diagnostic support for WSI analysis. Recent advances in foundational pathology models have increased the need for benchmarking tasks. The Camelyon series is one of the most widely used open-source datasets in computational pathology. However, the quality, accessibility, and clinical relevance of the labels have not been comprehensively evaluated. In this study, we reprocessed 1,399 WSIs and labels from the Camelyon-16 and Camelyon-17 datasets, removing low-quality slides, correcting erroneous labels, and providing expert pixel annotations for tumor regions in the previously unreleased test set. Based on the sizes of re-annotated tumor regions, we upgraded the binary cancer screening task to a four-class task: negative, micro-metastasis, macro-metastasis, and Isolated Tumor Cells (ITC). We reevaluated pre-trained pathology feature extractors and multiple instance learning (MIL) methods using the cleane
Accurate lymph node metastasis (LNM) assessment in rectal cancer is essential for treatment planning, yet current MRI-based evaluation shows unsatisfactory accuracy, leading to suboptimal clinical decisions. Developing automated systems also faces significant obstacles, primarily the lack of node-level annotations. Previous methods treat lymph nodes as isolated entities rather than as an interconnected system, overlooking valuable spatial and contextual information. To solve this problem, we present WeGA, a novel weakly-supervised global-local affinity learning framework that addresses these challenges through three key innovations: 1) a dual-branch architecture with DINOv2 backbone for global context and residual encoder for local node details; 2) a global-local affinity extractor that aligns features across scales through cross-attention fusion; and 3) a regional affinity loss that enforces structural coherence between classification maps and anatomical regions. Experiments across one internal and two external test centers demonstrate that WeGA outperforms existing methods, achieving AUCs of 0.750, 0.822, and 0.802 respectively. By effectively modeling the relationships between i
Do cancer cells escape their confinement of their original habitat in the primary tumor or are they forced out by ecological changes in their home niche? Describing metastasis in terms of a simple one-way migration of cells from the primary to target organs is an insufficient concept to cover the nuances of cancer spread. A diaspora is the scattering of people away from an established homeland. To date, diaspora has been a uniquely human term utilized by social scientists, however, the application of the diaspora concept to metastasis may yield new biological insights as well as therapeutic paradigms. The diaspora paradigm takes into account and models several variables: the quality of the primary tumor microenvironment, the fitness of individual cancer cell migrants as well as migrant populations, the rate of bidirectional migration of cancer and host cells between cancer sites, and the quality of the target microenvironments to establish metastatic sites. Ecological scientific principles can be applied to the cancer diaspora to develop new therapeutic strategies. For example, ecological traps, habitats that lead to the extinction of a species, can be developed to attract cancer c
Lymph node (LN) metastasis status is one of the most critical prognostic and cancer staging factors for patients with resectable pancreatic ductal adenocarcinoma (PDAC), or in general, for any types of solid malignant tumors. Preoperative prediction of LN metastasis from non-invasive CT imaging is highly desired, as it might be straightforwardly used to guide the following neoadjuvant treatment decision and surgical planning. Most studies only capture the tumor characteristics in CT imaging to implicitly infer LN metastasis and very few work exploit direct LN's CT imaging information. To the best of our knowledge, this is the first work to propose a fully-automated LN segmentation and identification network to directly facilitate the LN metastasis status prediction task. Nevertheless LN segmentation/detection is very challenging since LN can be easily confused with other hard negative anatomic structures (e.g., vessels) from radiological images. We explore the anatomical spatial context priors of pancreatic LN locations by generating a guiding attention map from related organs and vessels to assist segmentation and infer LN status. As such, LN segmentation is impelled to focus on r
With a high rate of morbidity and mortality, colorectal cancer (CRC) ranks third in mortality among cancers. By analyzing the texture properties of images and quantifying the heterogeneity of tumors, radiomics and radiogenomics are non-invasive methods to determine the biological properties of CRC. Recently, several articles have discussed the application of radiomics in different aspects of CRC. Therefore, given the large amount of data published, this review aims to discuss how radiomics can be used for distinguishing benign and malignant colorectal lesions, diagnosing, staging, predicting prognosis and treatment response, and predicting lymph node and hepatic metastasis of CRC, based on radiomic features extracted from magnetic resonance imaging (MRI), computed tomography (CT), esophageal ultrasonography (EUS), and positron emission tomography-CT (PET-CT). Challenges in bringing radiomics to clinical application and future solutions have also been discussed. With the progress made in radiomics and the application of deep and machine learning in this area, radiomics can become one of the main tools for the personalized management of CRC patients shortly.
Motivated by models of cancer metastasis, this paper introduces a type of (multi-type) branching process that records the positions of particles, representing tumor cells or clusters. Particles may be absorbed (removed from the state space), move, or settle. The process is rigorously constructed, and the Markov property is established via embedding into a multidimensional process that tracks the labels, positions, and phases (moving or resting) of living particles. The Feller property for the associated semigroup is investigated. It is proved for a simplified model that tracks the number of particles in each class, and an explicit generator is derived, enabling Feynman-Kac-type formulas in this framework.
In recent years, cancer genome sequencing and other high-throughput studies of cancer genomes have generated many notable discoveries. In this review, Novel genomic alteration mechanisms, such as chromothripsis (chromosomal crisis) and kataegis (mutation storms), and their implications for cancer are discussed. Genomic alterations spur cancer genome evolution. Thus, the relationship between cancer clonal evolution and cancer stems cells is commented. The key question in cancer biology concerns how these genomic alterations support cancer development and metastasis in the context of biological functioning. Thus far, efforts such as pathway analysis have improved the understanding of the functional contributions of genetic mutations and DNA copy number variations to cancer development, progression and metastasis. However, the known pathways correspond to a small fraction, plausibly 5-10%, of somatic mutations and genes with an altered copy number. To develop a comprehensive understanding of the function of these genomic alterations in cancer, an integrative network framework is proposed and discussed. Finally, the challenges and the directions of studying cancer omic data using an in
Can we predict if an early stage cancer patient is at high risk of developing distant metastasis and what clinicopathological factors are associated with such a risk? In this paper, we propose a ranking based censoring-aware machine learning model for answering such questions. The proposed model is able to generate an interpretable formula for risk stratifi-cation using a minimal number of clinicopathological covariates through L1-regulrization. Using this approach, we analyze the association of time to distant metastasis (TTDM) with various clinical parameters for early stage, luminal (ER+ or HER2-) breast cancer patients who received endocrine therapy but no chemotherapy (n = 728). The TTDM risk stratification formula obtained using the proposed approach is primarily based on mitotic score, histolog-ical tumor type and lymphovascular invasion. These findings corroborate with the known role of these covariates in increased risk for distant metastasis. Our analysis shows that the proposed risk stratification formula can discriminate between cases with high and low risk of distant metastasis (p-value < 0.005) and can also rank cases based on their time to distant metastasis with
Predicting TNM stage is the major determinant of breast cancer prognosis and treatment. The essential part of TNM stage classification is whether the cancer has metastasized to the regional lymph nodes (N-stage). Pathologic N-stage (pN-stage) is commonly performed by pathologists detecting metastasis in histological slides. However, this diagnostic procedure is prone to misinterpretation and would normally require extensive time by pathologists because of the sheer volume of data that needs a thorough review. Automated detection of lymph node metastasis and pN-stage prediction has a great potential to reduce their workload and help the pathologist. Recent advances in convolutional neural networks (CNN) have shown significant improvements in histological slide analysis, but accuracy is not optimized because of the difficulty in the handling of gigapixel images. In this paper, we propose a robust method for metastasis detection and pN-stage classification in breast cancer from multiple gigapixel pathology images in an effective way. pN-stage is predicted by combining patch-level CNN based metastasis detector and slide-level lymph node classifier. The proposed framework achieves a sta
Distant metastasis is the major cause of death in colorectal cancer (CRC). Patients at high risk of developing distant metastasis could benefit from appropriate adjuvant and follow-up treatments if stratified accurately at an early stage of the disease. Studies have increasingly recognized the role of diverse cellular components within the tumor microenvironment in the development and progression of CRC tumors. In this paper, we show that a new method of automated analysis of digitized images from colorectal cancer tissue slides can provide important estimates of distant metastasis-free survival (DMFS, the time before metastasis is first observed) on the basis of details of the microenvironment. Specifically, we determine what cell types are found in the vicinity of other cell types, and in what numbers, rather than concentrating exclusively on the cancerous cells. We then extract novel tissue phenotypic signatures using statistical measurements about tissue composition. Such signatures can underpin clinical decisions about the advisability of various types of adjuvant therapy.
Deep learning has been shown to be useful to detect breast cancer metastases by analyzing whole slide images of sentinel lymph nodes. However, it requires extensive scanning and analysis of all the lymph nodes slides for each case. Our deep learning study focuses on breast cancer screening with only a small set of image patches from any sentinel lymph node, positive or negative for metastasis, to detect changes in tumor environment and not in the tumor itself. We design a convolutional neural network in the Python language to build a diagnostic model for this purpose. The excellent results from this preliminary study provided a proof of concept for incorporating automated metastatic screen into the digital pathology workflow to augment the pathologists' productivity. Our approach is unique since it provides a very rapid screen rather than an exhaustive search for tumor in all fields of all sentinel lymph nodes.