Abstract A07: Gene analysis maps HCC heterogeneity and orientates personalized therapy

Hepatocellular carcinoma (HCC) has variable prognosis depending both on the severity of underlying liver disease and of its biological characteristic. We recently identified, in a prospective series of HCCs at first presentation, a 5-genes transcriptomic signature, which accurately and significantly predicts growth speed and survival (Gut. 2015 Feb 9. pii:gutjnl-2014-308483. doi: 10.1136/gutjnl-2014-308483). This signature encounters 5 up-regulated genes (ANGPT2, DLL4, NETO2, ESM1, NR4A1), all associated with neo-angiogenesis. Such gene analysis prompted us to characterize further the molecular pathways underlying tumor aggressiveness and consequently clinical outcome.The cohort of 78 prospectively identified HCCs was further characterized. Transcriptomic analysis was performed by microarray experiments (Agilent Technologies, Palo Alto, CA; Genomics Service Department of Miltenyi Biotec GmbH Bergisch Gladbach, Germany). Circulating cytokines were measured using human Quantikine® ELISA kit (R&D Systems, Minneapolis, MN, USA). For PD-1 and PD-L1 immunohistochemistry, samples were incubated with mouse monoclonal antibody (Ventana), for 24 minutes at 37°C. Biological data were analyzed according to HCC growth speed and patients’ survival.Genes down- or up-regulated affected prognosis and survival. In particular, the worst survival was correlated with down-regulation of CLEC4G and CLEC1B and up-regulation of MMP1, MMP10, MMP12 and WNT11. Next, we also measured a ...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Cancer Niche / Cellular Interactions: Poster Presentations - Proffered Abstracts Source Type: research