Platelet activation and the release of various growth factors from platelet granules in response to tumor cell profoundly influence tumor biology. Platelet hyperreactivity in cancer patients is a frequently discussed phenomenon; however, cancer patients were also found to have platelet dysfunction. Considerably less is known about exhaustion of platelet kinetics in cancer.
In this study, we investigated kinetics of intra-platelet growth factors in hepatocellular carcinoma (HCC) recurrence. We prospectively recruited forty patients diagnosed with HCC who were undergoing liver resection. The patients were followed every three months with imagings after the resection. Platelet fractions were separately isolated before and after a month of radical resection of the tumor. Growth factors/cytokines were measured using enzyme-linked immunosorbent assay (ELISA) kits. Follow-up was standardized to two years. HCC recurrence was diagnosed on the basis of imaging.
Fifteen patients developed post-resection HCC recurrence during 2-year follow-up. The concentrations of platelet-alpha granules secreted growth factors [vascular endothelial growth factor-A (VEGF-A), angiopoietin-1(Ang-1)] and dense granules secreted growth factors (serotonin) were significantly depleted in patients with early HCC recurrence. In addition, the post-resection platelet count was also significantly lower in patients with recurrence than those without recurrence. A combined receiver-operating characteristic (ROC) curve generated to determine the cut-off values for these growth factors yielded both specificity and sensitivity of greater than 80%, area under curve (AUC) > 0.8, and P < 0.001. Furthermore, in the binary logistic regression model, VEGF-A was able to independently predict early HCC recurrence (P < 0.05); accordingly, the disease-free interval was substantially worse in accordance with the exhausted intra-platelet growth factors.
We found a qualitative and quantitative platelet crisis, and its prognostic implication in patients with post-resection HCC recurrence. This study provides an avenue to identify the pathophysiological mechanism of the impaired platelet-kinetics and its relevance in cancer biology.
Clinical trial identification
Legal entity responsible for the study
Japan Society for the Promotion of Science (JSPS).
All authors have declared no conflicts of interest.