Jadwal Sholat

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Ilmu Komputer & AI editorial

Open AccessOA2026

Liquid Biopsy in Colorectal Cancer: Future Perspectives Through the Lens of Artificial Intelligence—A Comprehensive Review of Novel Literature

A narrative review of ctDNA, CTCs, and AI-driven analytics for precision oncology in colorectal cancer
D. Păduraru; A. Palcău; G. Gorecki; A. Dinulescu; Maria-Luiza Baean· International Journal of Molecular Sciences· 2026· DOI 10.3390/ijms27093951

The core problem

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, with prognosis critically dependent on the stage at diagnosis. Traditional tissue biopsy presents well-known limitations, including tumor heterogeneity and invasiveness. Liquid biopsy, encompassing the analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and other cell-free biomarkers, has emerged as a transformative approach for non-invasive tumor profiling. This comprehensive narrative review outlines the recent evidence published on the current state and future perspectives of liquid biopsy in CRC, with a focused emphasis on the role of artificial intelligence (AI), machine learning (ML), and deep learning (DL) in data analysis and clinical translation. The review aims to synthesize novel literature from January 2020 to January 2026, highlighting how AI-driven analytical frameworks augment the sensitivity and specificity of liquid biopsy interpretation and enable multimodal data integration.

Innovation

Liquid biopsy platforms, particularly ctDNA sequencing and methylation profiling, demonstrate increasing clinical utility across the CRC care continuum from population screening to post-surgical minimal residual disease (MRD) detection and real-time therapy monitoring. AI-driven analytical frameworks, including Random Forest, Convolutional Neural Networks, LSTM models, and more recently Large Language Models (LLMs), substantially augment the sensitivity and specificity of liquid biopsy interpretation, enabling multimodal data integration. For example, ctDNA analysis has shown high concordance with tissue genotyping for key mutations such as KRAS, NRAS, and BRAF, and methylation signatures have achieved high accuracy in early CRC detection. AI models have improved the detection of MRD with limits of detection below 0.01% variant allele frequency. The integration of AI with liquid biopsy data has also facilitated the prediction of treatment response and resistance mechanisms, with several studies reporting area under the curve (AUC) values exceeding 0.90 for ML-based classifiers. The table below summarizes key performance metrics from selected studies.

| Biomarker | AI Method | Perf

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, with prognosis critically dependent on the stage at diagnosis. Traditional tissue biopsy presents well-known limitations, including tumor heterogeneity and invasiveness. Liquid biopsy, encompassing the analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes, and other cell-free biomarkers, has emerged as a transformative approach for non-invasive tumor profiling. This comprehensive narrative review outlines the recent evidence published on the current state and future perspectives of liquid biopsy in CRC, with a focused emphasis on the role of artificial intelligence (AI), machine learning (ML), and deep learning (DL) in data analysis and clinical translation. The review aims to synthesize novel literature from January 2020 to January 2026, highlighting how AI-driven analytical frameworks augment the sensitivity and specificity of liquid biopsy interpretation and enable multimodal data integration.
A narrative review of the literature was conducted by searching PubMed/MEDLINE, EMBASE, and ClinicalTrials.gov for articles published between January 2020 and January 2026, using a predefined Boolean search string combining terms related to liquid biopsy biomarkers, colorectal cancer, and artificial intelligence methodologies. Filters were applied to include only English-language human studies. Additional relevant sources were consulted to ensure comprehensive coverage of the available literature. The search strategy focused on identifying studies that reported on liquid biopsy platforms, particularly ctDNA sequencing and methylation profiling, and their clinical utility across the CRC care continuum. Studies employing AI, ML, and DL techniques for liquid biopsy data analysis were prioritized. The review also examined emerging technologies such as federated learning and large language models (LLMs) for clinical decision support.

Why it matters

The convergence of liquid biopsy technology and AI-driven analytics represents a paradigm shift toward precision oncology in CRC. AI algorithms can integrate multimodal data—genomic, transcriptomic, proteomic, and clinical—to provide a holistic view of tumor dynamics. However, remaining challenges include analytical standardization, model explainability, regulatory harmonization, and equitable access. The lack of standardized protocols for sample collection, processing, and sequencing can lead to variability in results, hindering clinical implementation. AI models, particularly deep learning, often operate as black boxes, raising concerns about trust and accountability in clinical decision-making. Regulatory frameworks are still evolving to address the unique challenges of AI-based diagnostics. Moreover, equitable access to these technologies is crucial to avoid exacerbating health disparities. Future integration of federated learning frameworks and LLM-based clinical decision support tools will be essential for responsible clinical translation. Federated learning allows model training across multiple institutions without sharing raw data, addressing privacy concerns. LLMs can synthesize vast amounts of literature and patient data to assist oncologists in real-time decision-making. The following Mermaid diagram illustrates the workflow of liquid biopsy combined with AI for CRC management:

Mathematically, the integration of AI with liquid biopsy can be represented as a function that maps high-dimensional biomarker data to clinical outcomes:

where represents the multimodal biomarker data, are the model parameters learned from training data, and is the error term. The goal is to minimize the loss function

over a training set. For classification tasks, such as cancer detection, the model outputs a probability . Advanced architectures like CNNs for image-based CTC analysis or LSTMs for sequential ctDNA measurements can capture complex patterns. The future lies in developing interpretable AI models that can provide insights into the biological mechanisms underlying the predictions, thereby enhancing clinical trust and facilitating regulatory approval.

Who should read this

CS practitioners and researchers

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