Deciphering Platelet Kinetics in Diagnostic and Prognostic Evaluation of Hepatocellular Carcinoma

Abstract

Liver pathophysiology can, directly and indirectly, impose morphological or biochemical abnormalities of the platelets. Conversely, platelets are also able to regulate the promitogenic and profibrotic signals on liver pathobiology. Platelet contribution to the liver pathophysiology is typically facilitated by the platelet-derived growth factors that are sequestered in different subsets of alpha and dense granules, and the release of these growth factors is synchronized according to the stage and type of liver disease or injury. Thus, platelets harbor clinically relevant information with potential diagnostic and prognostic implications in liver diseases. Hepatocellular carcinoma (HCC) largely influences the platelet kinetics, and a growing body of evidence has recognized its association with HCC occurrence or prognosis. This narrative review summarizes the progress made on implicating platelet as a diagnostic and prognostic tool for HCC; the review also dissects the contradictory results from earlier studies and reflects how combining platelet-based information may enable more reliable test for diagnostic and prognostic evaluation of HCC.

Platelets and Hepatocellular Cancer: Bridging the Bench to the Clinics

“…Serotonin regulates a wide range of physiological and pathophysiological processes, acting as a ligand for a large family of 5-HT receptors. Platelets’ dense granules contain about 95% of total plasma serotonin, releasing it in response to different stimuli [42]. Serotonin is a potent angiogenic factor in driving tumor angiogenesis, a potent mitogen for hepatocytes, and it is crucial for liver regeneration.…”

“…The epidermal growth factor (EGF) is synthesized in the megakaryocytes, being mostly present in the alpha granules of human platelets [42]. EGF is directly associated with the inflammatory microenvironment, also regulating HCC proliferation, migration, and metastatic potential of cancer cells (Figure 1 and Table 2) [52,53,54,55].…”

“…Vascular endothelial growth factor (VEGF) represents a critical driving force for physiological and pathological angiogenesis. VEGF is largely sequestered in the platelets, and platelets act as a significant physiological transporter of this growth factor in the circulation (Figure 1) [42].…”

A novel model for predicting posthepatectomy liver failure in patients with hepatocellular carcinoma

“…A majority of patients diagnosed with HCC were accompanied with underlying liver fibrosis or cirrhosis. Distortion of the normal liver architecture and formation fibrous septum in patients with liver cirrhosis would increase the resistance to portal vein flow, resulting in portal hypertension, hypersplenism, and resultant thrombocytopenia[6, 7]. Platelet count was reported to be a simple but useful indicator of liver cirrhosis and function of spleen[8].…”

Predictive Value of Diminished Serum PDGF-BB after Curative Resection of Hepatocellular Cancer

“…Platelet-related biomarkers, detected in the circulation (whole blood, serum, or plasma), have long been considered as a potential diagnostic tool in cancer[3–7]. These growth factors have demonstrated several implications in the field of oncology including screening, diagnostic, and prognostic relevance of diseases[7]. Platelet-related growth factors reflect paradoxical association with different physiological and pathological events[8].…”