title: Platelets contribute to growth and metastasis in hepatocellular carcinoma.
abstract: To determine the association of platelets with hepatocellular carcinoma (HCC) growth and its metastasis. We examined platelets, laboratory, and radiological data of consecutive 420 HCC and 1008 cirrhosis cases. Follow-up information of platelet count in cirrhosis to HCC, pre- to post-therapy, and post-therapy to HCC outcome was analyzed. Cytokine profiling was performed in HCC and cirrhosis (n = 10 each). On the basis of imaging, HCC was divided into six subgroups. Cytosmears of HCC were assessed for platelet clustering around tumor cells. An in vitro Matrigel invasion assay was performed on human HCC cell lines using graded concentration of platelets. Baseline platelet numbers and platelet/lymphocyte ratios (PLRs) were significantly higher (p < 0.001) in HCC than cirrhosis. IL-1, IL-6, FGF, G-CSF, thrombopoietin, and VEGF were higher in HCC than cirrhosis. Platelet counts were increased after HCC conversion of cirrhosis (p < 0.001) and decreased (p < 0.001) after therapy. Platelets and PLR in recurrence cases were higher than in responders at baseline. AFP, PIVKAII, platelets, and PLR increase (p < 0.001 each) with advancement in HCC growth. Multivariate analysis showed platelets (p = 0.002), PLR (p = 0.004), and AFP (p < 0.001) associated with distant metastasis. Platelet clustering seen in 75.7% of HCC group 3, 45% in group 2, and 12.5% in group 1 cases (p < 0.001). Invaded cells in Matrigel assay positively correlated with platelet concentration. Platelets can contribute to the development, growth, invasion, and metastasis of HCC. Rising platelet count after HCC therapy is indicative of incomplete response or recurrence.
authors.affiliation: Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Chhagan
authors.initials: C
authors.lastname: Bihari
authors.affiliation: Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Rastogi
authors.affiliation: Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Saggere Muralikrishna
authors.initials: SM
authors.lastname: Shasthry
authors.affiliation: Department of Tranfusion Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Meenu
authors.initials: M
authors.lastname: Bajpai
authors.affiliation: Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Ajeet Singh
authors.initials: AS
authors.lastname: Bhadoria
authors.affiliation: Department of Radiology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: S
authors.initials: S
authors.lastname: Rajesh
authors.affiliation: Department of Radiology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Amar
authors.initials: A
authors.lastname: Mukund
authors.affiliation: Department of Research, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Anupam
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
authors.forename: Shiv K
authors.initials: SK
authors.lastname: Sarin
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D016207:Cytokines / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology*; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D010976:Platelet Count
chemical_list: D016207:Cytokines
keywords: Hepatocellular carcinoma; cirrhosis; metastasis; platelets