Novel serum biomarkers for real-time treatment monitoring and prognostication in hepatocellular carcinoma patients

Background: Alpha-fetoprotein is limited in terms of being able to monitor the progression of hepatocellular carcinoma (HCC) after receiving local or systemic treatments. Other potentially useful serum-based biomarkers for HCC, such as des-gamma-carboxy prothrombin (DCP), Golgi protein 73 (GP73), osteopontin (OPN), heat shock protein 70 (HSP70), and neutrophil-to-lymphocyte ratio (NLR), were compared to AFP in terms of their ability to determine response to treatment and prognosis following transarterial chemoembolisation (TACE) and sorafenib therapies. Methods: As part of a prospective study on patients with intermediate HCC treated with TACE (n=86) or sorafenib (n=62), 148 patients were enrolled. Baseline, week 4, week 8, and radiologic progression serum samples were collected. The kinetics of the biomarkers were correlated with mRECIST response and overall survival (OS). The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the biomarkers' ability to detect residual disease and predict progression. Results: For the detection of post-TACE residual disease, HSP70 had the highest sensitivity among the biomarkers evaluated (88%), followed by GP73 (84%). In the monitoring setting during sorafenib therapy, DCP and OPN were independently predictive of progression (AUCs: 0.86 and 0.83, respectively). Using overall results, the combination of DCP, GP73, OPN, and HSP70 yielded a composite panel with 92% specificity for early progression detection (AUC: 0.93). Patients with persistently elevated biomarkers (i.e., ≥3 markers) at the 8-week visit had a significantly lower median OS than those without the same number of elevated markers (6.2 vs 16.8 months, p<0.001). Conclusion: Novel serum biomarkers, particularly DCP for sorafenib monitoring, HSP70 and GP73 for post-TACE residual disease detection, and OPN for tumour burden tracking, may improve real-time treatment monitoring and prognostication in HCC, outperforming AFP across multiple therapeutic contexts.