Abstract
Background: Improving surgical outcomes in hepatocellular carcinoma (HCC) patients would greatly benefit from biomarkers. Angiogenesis and inflammation are hallmarks of HCC progression and therapeutic targets. Methods: We retrospectively evaluated preoperative clinical variables and circulating (plasma) biomarkers of angiogenesis and inflammation in a cohort of HCC patients who underwent liver resection (LR) or transplantation (LT). Biomarker correlation with outcomes—freedom of liver recurrence (FLR), disease-free survival (DFS) and overall survival (OS)—was tested using univariate and multivariate Cox regression analyses. Results: Survival outcomes associated with sVEGFR1, VEGF and VEGF-C in LT patients and with IL-10 in LR patients. Moreover, in LT patients within Milan criteria, higher plasma VEGF and sVEGFR1 were associated with worse outcomes, while in those outside Milan criteria lower plasma VEGF-C associated with better outcomes. Multivariate analysis indicated that adding plasma VEGF or VEGF-C to a predictive model including Milan criteria and AFP improved prediction of DFS and OS (all p < 0.05). Conclusion: Survival outcomes after LR or LT differentially associated with angiogenic and inflammatory biomarkers. High plasma VEGF correlated with poorer prognosis within Milan criteria while low plasma VEGF-C associated with better prognosis outside Milan criteria. These candidate biomarkers should be further validated to improve patient stratification.
Highlights
Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor and a leading cause of cancer-related death worldwide [1]
Patient characteristics are listed in 64 years for liver resection (LR) patients versus 57 years for liver transplantation (LT) patients (p < 0.0001, see Table 1)
We found no difference in overall survival (OS), disease-free survival (DFS) or plasma vascular endothelial growth factor (VEGF), VEGF-C or AFP biomarker levels between hepatocellular carcinoma (HCC) patients within versus those outside Milan criteria (Table S2)
Summary
Hepatocellular carcinoma (HCC) is the fifth most common malignant tumor and a leading cause of cancer-related death worldwide [1]. Multiple studies have shown that some patients within Milan criteria may have a poor outcome Despite these strict criteria, the 5-year recurrence rate after LT remains approximately 10–15% for HCC. Improving surgical outcomes in hepatocellular carcinoma (HCC) patients would greatly benefit from biomarkers. Methods: We retrospectively evaluated preoperative clinical variables and circulating (plasma) biomarkers of angiogenesis and inflammation in a cohort of HCC patients who underwent liver resection (LR) or transplantation (LT). High plasma VEGF correlated with poorer prognosis within Milan criteria while low plasma VEGF-C associated with better prognosis outside Milan criteria. These candidate biomarkers should be further validated to improve patient stratification
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