Affiliations: Liver Unit, Department of Internal Medicine, Hospital
Universitari Vall d'Hebrón, Barcelona, Spain | Centro de Investigación Biomédica en Red de
Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto Carlos III,
Spain | Liver Cancer Program, Division of Liver Diseases,
Mount Sinai School of Medicine, New York, NY, USA | Department of General-, Visceral- and Pediatric
Surgery, University Hospital Düsseldorf, Düsseldorf, Germany
Abstract: Hepatocellular carcinoma (HCC) is one of the most lethal cancers
worldwide, representing also the main cause of death among cirrhotic patients.
In contrast to most other solid tumors, the underlying cirrhotic liver disease
in HCC patients greatly impairs tumor related prognosis, conferring this
neoplasm a unique situation, in which accurate prognostic prediction is a
relevant and unmet need. Although clinical staging systems have improved
significantly and now comprise tumor characteristics, liver function and
patient performance status, the integration of molecular data into these
algorithms is still hypothetical. Molecular profiling of HCC has led to a
better understanding of the physiopathology of this neoplasm and has allowed
developing novel therapeutic approaches (e.g. molecular targeted therapies)
for a tumor previously considered as therapy-refractory. Integrative analysis
of different reported genomic datasets has revealed common subclasses between
different studies, highlighting their biological relevance in HCC. Gene
signatures derived from tumors and from the adjacent tissue have been able to
differentiate subclasses with different outcomes and have been proposed as
potential predictive markers in the clinical setting. Genomic characterization
of surrounding non-tumor tissue might be of particular interest to identify
patients at high risk of developing HCC and therefore to select those patients
that would benefit of potential chemopreventive strategies. Epigenetic analyses
(methylation and miRNA profiling) are adding up to the knowlegde derived from
gene expression data and should not be forgotten in the molecular diagnosis of
HCC. Integrative analyses of genetic and epigenetic information of the tumor
and the surrounding tissue should be used to identify novel biomarkers and
therapeutic targets in HCC, to improve existing treatment algorithms and to
eventually design a more personalized medicine in this devastating disease.
