A temporal keyword co-occurrence network mining framework for detecting structural transitions in cancer biomarker...

Biomarker research for cancer diagnosis and prognosis has rapidly expanded technologically and thematically, along with advancements in molecular diagnostics, liquid biopsy, immunotherapy, and artificial intelligence (AI)-based technologies. However, few studies have systematically structured these technological transitions and research framework changes using time-series analyses. Accordingly, this study treated cancer biomarker research as a large-scale biological knowledge system and aimed to examine the structural transitions and patterns of technological evolution through a temporal network-based analysis. Using the Web of Science database, 149,419 papers on cancer diagnosis and prognostic biomarkers were collected over three periods (2006-2011, 2012-2017, and 2018-2023). For each period, 500 core keywords were extracted using the weighted PageRank algorithm, and keyword co-occurrence networks were analyzed to identify temporal changes in the network structure indicators. Clustering was performed based on integrated keywords and evolutionary patterns were analyzed through research intensity and openness measurements. An attribute-based overlay analysis was conducted, along with analyses of keyword retention/turnover rates. Biomarker research has evolved from pathology-based diagnostic technology (2006-2011) and liquid biopsy-based noninvasive diagnostic technology (2012-2017) to AI- and immune-based precision medicine (2018-2023). Network structure analysis revealed an increased density and clustering of keyword connections over time, with expanded inter-cluster connections, indicating research topic convergence and increased structural complexity. Cluster 3 (Immune/AI-based Precision Medicine) exhibited the highest keyword turnover rate (0.545), emerging as a recent research focus, whereas Cluster 1 (Solid Tumor Pathology/Molecular Mechanisms) maintained stability with high keyword retention and a low change rate. This study introduces a temporal keyword co-occurrence network framework for detecting structural transitions in cancer biomarker research, providing an analytical perspective that complements conventional frequency-based bibliometric approaches. These findings offer quantitative insights into the technological complexity and convergent patterns of research development, reflected in increasing inter-cluster connectivity and integrated research trajectories in cancer diagnostic and prognostic biomarkers.