Elsevier

Journal of Hepatology

Volume 44, Issue 4, April 2006, Pages 798-805
Journal of Hepatology

Review
Molecular prognostication of liver cancer: End of the beginning

https://doi.org/10.1016/j.jhep.2006.01.008Get rights and content

Introduction

New technological developments have frequently preceded major advances in biomedical research and medicine [1]. For example, the development of fluorescent DNA sequencing techniques made it possible to establish the large-scale high-throughput technology needed for human genome sequencing. Polymerase chain reaction (PCR), fluorescent DNA sequencing, and other techniques have enabled the discovery of about 1700 mendelian disease genes [2]. The advent of the DNA microarray based technologies has now made it possible to measure simultaneously the expression of tens of thousands of genes in different tissues under a variety of conditions. This high-throughput technology has afforded biomedical scientists a unique opportunity to integrate the descriptive characteristics (i.e. ‘phenotype’) of a biological system under study with the genomic readout (i.e. gene expression). The opportunity to contemplate the integrated view of biological systems has provoked a shift in biological sciences away from the classical reductionism to systems biology [1], [3], [4]. The systems approach to a disease is based on the hypothesis that disease processes perturb a regulatory network of genes and proteins in a way that differs from the respective normal counterpart. Consequently, by using multi-parametric measurements it may be possible to transform current diagnostic and therapeutic approaches and enable a predictive and preventive personalized medicine [4].

The application of microarray technologies to characterize tumors at the gene expression level has significantly impacted clinical oncology [5], [6]. Global gene expression analysis of various human tumors has resulted in the identification of gene expression patterns or signatures related to tumor classification, disease outcome and response to therapy. The microarray technology has also been used to investigate the mechanism of action of specific cancer therapeutics. In this review, we will briefly discuss the general impact of the global gene expression analysis on cancer research and devote the rest to the microarray based gene expression analysis of human hepatocellular carcinoma (HCC).

Section snippets

Tumor classification and prognostic prediction

It is well established that cancer even in the same tissue is a very heterogeneous disease that differs widely in clinical outcome and in response to therapy. It is now clear that this heterogeneity is due to different molecular defects that can induce similar tumor phenotypes. Although, histopathological and biochemical markers constitute important tools for identifying groups of tumors that differ with respect to prognosis and responses to treatments, the genes and molecular pathways

Predicting HCC prognosis

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, accounting for an estimated 600,000 deaths annually [17]. While HCC is common in southeast Asia and sub-Sahara Africa, the incidence rates of HCC have continued to increase in the United States and western Europe over the past 25 years and the incidence and mortality rates of HCC are expected to double over the next 10–20 years [18], [19], [20]. Although much is known about both the cellular changes that lead to HCC

Molecular profiling of HCC

Numerous studies dealing with gene expression profiling of HCC have appeared during the last 5 years (see Table 1). In addition, several review articles addressing the application of the DNA microarray platform in studies on HCC have recently been published [35], [36], [37], [38], [39]. The molecular profiling of HCC presents challenges that are not commonly seen in other human tumors. This is primarily due to the complex pathogenesis of this cancer [23]. HCC arises most commonly in cirrhotic

Survival

It has long been recognized that survival prediction of HCC patients is more challenging than with most other cancers. This is, in the cases of HBV and HCV, the consequence of the underlying viral driven non-neoplastic disease, i.e. chronic hepatitis and cirrhosis that can and does inflict functional impairment on the liver that may affect the outcome of the HCC patients. However, in a recent study on survival of HCC patients, it was demonstrated that the HCC was the prime cause of death in

Conclusion and perspective

Profiling liver cancer and indeed cancer in general with gene expression arrays has become common. The results from early studies, particularly those unraveling novel cancer classifications and identifying novel markers for prediction of clinical outcome, kindled the hope that this technology would provide understanding of the molecular differences between clinical cases and allow individualization of care. There can be no doubt that the DNA microarray technology has provided an extraordinary

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