A Specialized Importance-Aware Quantum Convolutional Neural Network with Ring-Topology (IA-QCNN) for MGMT Promoter Methylation Prediction in Glioblastoma
Authors: Emine Akpinar, Murat Oduncuoglu
Organizations: Department of Physics, Yildiz Technical University, Istanbul, Turkey
GBM is a highly aggressive primary malignancy in adults, necessitating personalized therapeutic strategies due to its inherent molecular heterogeneity. MGMT promoter methylation is a pivotal prognostic biomarker for anticipating response to temozolomide-based chemotherapy. Although various AI frameworks have been developed for non-invasive MGMT prediction, spatial heterogeneity of methylation status and the high-dimensional and correlated nature of MRI data frequently constrain discriminative feature learning and generalizability of classical models. To circumvent these limitations, a specialized IA-QCNN architecture is proposed, based on the principles of quantum mechanics, including superposition and entanglement, and enabling more efficient representation learning in high-dimensional Hilbert space. The framework establishes a methodological bridge between GBM radiogenomics and quantum deep learning by integrating energy-based slice selection, importance-aware weighting, ring-topology quantum convolution, and folding-based pooling layers. When the model predicts MGMT promoter methylation status using both mpMRI and T1Gd images, experimental results demonstrate that the IA-QCNN achieves high accuracy despite its low number of trainable parameters while effectively minimizing the overfitting problem observed in classical models. Quantitative analyses reveal that the T1Gd modality possesses higher discriminative power than mpMRI, establishing a clinically significant sequence preference. Furthermore, the model exhibits exceptional robustness in hybrid noise environments, effectively utilizing noise as a regularization mechanism to enhance predictive performance. Consequently, the specialized IA-QCNN architecture provides a robust and computationally efficient alternative to classical approaches in the analysis of heterogeneous radiogenomic data.
Background: Radiogenomics allows identification of radiological biomarkers for genomic phenotypes. In glioblastoma, these biomarkers could potentially complement patient stratification strategies. We aim to develop and analytically validate radiological biomarkers that capture immune cell signatures within IDH-wildtype glioblastoma microenvironment using radiogenomic analysis. Methods: This was a retrospective multicenter study using curated open-access anonymized imaging and genomic data from TCGA-GBM, CPTAC, IvyGAP, REMBRANDT and CGGA datasets. Imaging data consisted of MRI-based radiomic features extracted from necrotic core, enhancing and edema regions of deep learning-based auto-segmented tumors. Radiomic feature selections were performed using nested cross-validated LASSO. Support vector machine and ensemble models were trained using seventeen immune and cell-specific score labels extracted from deconvoluted transcriptomic data using pan-cancer and glioblastoma immune signature matrices as reference standards. Seventeen classifier models trained in three cross-cohort strategies were validated on three held-out datasets assessing stability and generalizability. Results: One-hundred-and-seventy-six patients were included in the study. The immune-related radiomic signatures obtained after feature selection were shape, first order and higher order radiomic features. Models predicting macrophage subtype immune signature showed stable mean performance on balanced accuracy (0.67) and precision (0.89) metrics for three independent holdout datasets with ensemble model outperforming support vector machine model. Conclusion: Radiogenomic models non-invasively predicted the macrophage subtype M0 immune signature in IDH-wildtype glioblastoma. These biomarkers have the potential to stratify patients for immunotherapy within prospective glioblastoma clinical trials.
Breast cancer diagnosis through thermographic image analysis remains a critical challenge in medical AI, with classical deep learning approaches facing limitations in complex thermal pattern classification tasks. This paper presents a novel Hybrid Quantum Neural Network (HQNN) architecture that integrates quantum computing principles with classical convolutional neural networks for enhanced breast cancer classification. Our approach employs parameterized quantum circuits with multi-head attention mechanisms for quantum-aware feature encoding, coupled with classical convolutional layers for comprehensive pattern recognition. The quantum component utilizes a 4qubit variational circuit with strongly entangling layers, while the classical component incorporates advanced attention mechanisms for feature fusion. Experimental validation on breast cancer thermographic data demonstrates substantial performance improvements over state-of-the-art classical architectures, with the quantum-enhanced approach exhibiting superior convergence dynamics and enhanced feature representation capabilities. Our findings provide evidence for quantum advantage in medical image classification through classical simulation, establishing a framework for quantum-classical hybrid systems in healthcare applications. The methodology addresses key challenges in quantum machine learning deployment while maintaining computational feasibility on near-term quantum devices.
Riza Alaudin Syah, Irwan Alnarus Kautsar, Gunawan Witjaksono +1
Quantum machine learning offers a promising new paradigm for computational biology by leveraging quantum mechanical principles to enhance cancer classification, biomarker discovery, and bioinformatics diagnostics. In this study, we apply QML to identify subtype specific biomarkers for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two predominant forms of non-small cell lung cancer. Our methodology involves a two-phase process: in Phase 1, differential expression analysis and methylation analysis between tumor and normal samples allows us to identify LUAD-specific and LUSC-specific genes, revealing potential prognostic biomarkers for cancer subtypes. Phase 2 focuses on developing a quantum classifier capable of distinguishing between LUAD and LUSC tumors, as well as between tumor and normal samples. This classifier not only enhances diagnostic precision but also demonstrates the quantum advantage in processing large-scale multiomic datasets. Our results consistently demonstrated that Sample3, representing the combined gene set, achieved the highest overall predictive performance in all metrics. These results demonstrate that QML provides an effective and scalable approach for biomarker discovery and subtype specific cancer classification. GO enrichment analysis highlighted the significant involvement of genes in synaptic signaling, ion channel regulation, and neuronal development. In the quantum phase, KEGG analysis further identified enrichment in cancer-associated pathways, including neurotrophin, MAPK, Ras, and PI3KAkt signaling, with key genes such as NGFR, NTRK2, and NTF3 suggesting a central role in neurotrophinmediated oncogenic processes. Our findings highlight the growing potential of quantum computing to advance precision oncology and next-generation biomedical analytics.