Validation of the biomarker toolkit using diagnostic colorectal cancer biomarkers – an evidence-based tool to support clinical adoption of biomarkers

BACKGROUND: Biomarkers offer valuable insights into diseases and bodily functions, yet many fail to achieve clinical implementation. Our recent research revealed a substantial translational gap, with only 0.94% of prognostic breast cancer biomarkers and 0.14% of diagnostic colorectal cancer biomarkers reaching clinical practice. To address this challenge, we developed the Biomarker Toolkit, designed to enhance translational outcomes by identifying cancer biomarkers most likely to succeed and highlighting areas requiring further research. This study aims to validate the Toolkit using a new dataset of diagnostic colorectal cancer biomarkers. METHODS: Systematic literature searches were conducted to identify clinical studies for successful and stalled diagnostic colorectal cancer biomarker groups. 'Successful' biomarkers were defined as those approved for diagnostic use in colorectal cancer by regulatory bodies. For the stalled cohort, a random selection of biomarkers associated with > 5 publications was drawn from a previous review, until the number of clinical studies in each cohort was equal. Each clinical study was examined for the presence or absence of 125 attributes present in the Toolkit, with a binary score (1 or 0) assigned accordingly. Total and category scores were calculated and compared between the successful and stalled biomarker groups, using Mann Whitney U Test, binary logistic and Cox regression analyses. RESULTS: Using the Toolkit, successful diagnostic colorectal cancer biomarkers demonstrated significantly higher total scores compared to the stalled group (44.7% versus 25.1%, p < 0.001). Successful biomarkers exhibited higher clinical utility scores even before receiving regulatory approval (42.1% versus 20.2%, p < 0.001). Additionally, the frequency and diversity of clinical utility publications for successful biomarkers continued to rise beyond the initial five-year period following the first biomarker publication. CONCLUSIONS: This study provides independent validation of the Biomarker Toolkit, having been initially validated using prognostic breast cancer biomarkers. The significantly higher Toolkit scores observed in successful diagnostic colorectal cancer biomarkers, particularly in clinical utility, even before regulatory approval, underscore the Toolkit's strong potential for predicting translational success.