Page 171 - ebook HCC

168 PROGRAMME AND ABSTRACTS GENEVA, SWITZERLAND EASL HCC SUMMIT 169
FEBRUARY 13 - 16, 2014

GENE SIGNATURES AND PCR-ARRAYS: ARE
THEY OF PRACTICAL USE TODAY?

Andreas Teufel 1
1 Universitätsklinikum Regensburg, Regensburg, Germany
Corresponding author’s e-mail: andreas.teufel@ukr.de

Over the past decade multiple clinical relevant gene expression signatures have been References
reported in HCC. These studies reported potential value in diagnosis as well as prediction Nault JC, Zucman-Rossi J. Genetics of hepatocellular carcinoma: The next generation. J
of survival, metastatic spread, or recurrence after resection. However, considerable Hepatol. 60: 224-6, 2014.
heterogeneity across these signatures resulted in a diversity in numbers of genes and Teufel A, Marquardt JU, Staib F, Galle PR. Snapshot liver transcriptome in hepatocellular
differences in prognostic relevance. Thus, validation of these signatures in independent carcinoma. J Hepatol. 56: 990-2, 2012.
patient cohorts remained difficult. As a result, these signatures are still not integrated into Marquardt JU, Galle PR, Teufel A. Molecular diagnosis and therapy of hepatocellular
clinical routine diagnostics and clinical decision making. This may in particular be due carcinoma (HCC): an emerging field for advanced technologies. J Hepatol. 56: 267-75,
to cirrhotic tissue generally used as controls, being itself significantly altered compared 2012.
to normal liver tissue. Furthermore, cirrhosis may be induced by significantly differing
underlying chronic liver diseases. However, increased robustness in diverse patient
cohorts will be necessary for a successful translation of these signatures into clinical routine
testing. More robust signatures may in particular be achieved by (further) reduction of the
number of genes / parameters in gene signatures allowing to analyze these parameters
CLINICAL SPEAKERS ABSTRACTS gene expression, methylation or protein expression may also contribute to reproducibility CLINICAL SPEAKERS ABSTRACTS
in more robust technological approaches. Furthermore, recent reports have also
demonstrated that a successful integration of data from diverse biological layers such as
and stability of gene expression signatures in HCC. However, the development of
more integrative signatures will also rely on advances in the field of bioinformatics and
the development of more sophisticated integrative algorithms. Nevertheless, hallmark
signaling of tumors, well established for the majority of solid tumors, such as proliferative
signaling, resistance against cell death, immortality, pro-angiogenic signaling, activation
of invasive and metastatic programs as well as pro-inflammatory signaling could be
recapitulated for HCC. Recent work has further demonstrated that many gene expression
changes and mutations found in tumor genome sequencing experiments were overlapping
in common signaling pathways. These data suggest that focusing on superimposed
biological functions or signaling pathways rather than single genes may also be helpful
in identifying robust genetic signatures. In summary, although several genetic signatures
had significant predictive ability, the successful translation into and rigorous evaluation
for a clinical application is yet to be generated. Milestone steps to achieve this goal will
be successful data integration, data reduction but also precise clinical and histological
definition of patient cohorts to be studied for future signature development.