Morris JS, Hassan MM, Zohner YE, et al. - This study sought to evaluate whether measures of biological heterogeneity significantly improve prediction of hepatocellular carcinoma risk. Researchers offer an approach for constructing risk scores from circulating biomarkers that produce a global biological characterization of an individual patient’s disease. They obtained plasma samples prospectively from 767 patients with hepatocellular carcinoma (HCC) and 200 controls, and 317 proteins were quantified in a Clinical Laboratory Improvement Amendments–certified biomarker testing laboratory. The results demonstrate that HepatoScore-14 augments existing HCC staging systems, dramatically refining patient prognostic assessments and therapeutic decision making and enrollment in clinical trials. The findings suggest that underlying strategy provides a global biological characterization of disease, and can be used broadly to other disease settings and biological media.