Preface

Hepatocellular Carcinoma represents a leading cause of cancer death and a major health problem in developing countries. It has also become increasingly important with the increase in hepatitis C infection in developed countries.

Knowledge of hepatocellular carcinoma has progressed rapidly. This book is a compendium of papers written by experts to present the most up-to-date knowledge of hepatocellular carcinoma. We have decided to divide this book on Hepatocellular Carcinoma into two books because of the overwhelming number of excellent book chapters we received from scientists and clinicians from all parts of the world:- Hepatocellular Carcinoma – Basic Research, and Hepatocellular Carcinoma – Clinical Research.

Hepatocellular Carcinoma – Basic Research is divided into three sections: (I) Biomarkers / Therapeutic Target; (II) Carcinogenesis / Invasion / Metastasis; and (III) Detection / Prevention / Prevalence. There are 18 chapters in this book.

This book is an important contribution to the field of hepatocellular carcinoma with an emphasis on basic research. The intended readers of this book are scientists and clinicians who are interested in research on hepatocellular carcinoma. Epidemiologists, pathologists, hospital administrators and drug manufacturers will also find this book useful.

> **Dr. Wan-Yee Lau**  Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China

**Part 1** 

**Biomarker / Therapeutic Target** 

**Part 1** 

**Biomarker / Therapeutic Target** 

**1** 

Rou Li Zhou

 *China* 

**LAPTM4B: A Novel Diagnostic** 

**for Hepatocellular Carcinoma** 

 *School of Basic Medical Sciences, Peking University* 

**Biomarker and Therapeutic Target** 

The carcinogenesis and progression of hepatocellular carcinoma (HCC) are complicated processes which evolve through distinct stages associated with cumulative genomic alterations, which result in deregulation of proliferation, metastasis and recurrence, leading to poor prognosis. Despite the fact many new therapeutic and diagnostic strategies for cancer have been developed in recent years, the cure rate for HCC has not satisfactorily improved and biomarkers currently used for HCC diagnosis are not satisfactory in either

More than one thousand cancer-associated genes and proteins have been identified, but the pathogenesis of hepatocellular carcinoma is still incompletely understood. Identifying the as yet unknown pivotal genes and proteins will be critical for early diagnosis, effective monitoring and novel therapies for this highly aggressive cancer. In previous work we cloned and identified a novel HCC-associated gene (lysosomal protein transmembrane 4 beta, *LAPTM4B*). Its complementary mRNA is highly expressed in the vast majority of HCC samples as compared with paired noncancerous liver from the same patient (PNL), fetal liver, and normal liver (Shao et al., 2003). Over our past decade studies have demonstrated that the *LAPTM4B* gene and the LAPTM4B-35 protein which it encodes would be pivotal

diagnostic biomarkers and therapeutic targets for hepatocellular carcinoma.

**2.1 Identification and cloning of the** *LAPTM4B* **gene** 

**2.** *LAPTM4B***: A novel gene associated with hepatocellular carcinoma** 

To search for genes involved in deregulation of proliferation and aberrant differentiation for hepatocellular carcinoma, fluorescent-differential display was performed using human liver tissues, including adult liver, fetal liver, HCC and its paired samples of noncancerous liver from the same patient (paired noncancerous liver). A cDNA fragment, which was not a part of any known gene, was found from 110 differential display fragments obtained. This cDNA fragment was highly expressed in HCC, significantly expressed in fetal liver and the paired noncancerous liver, but showed very low expression in normal adult liver (JJ. Liu et al., 2000). Cloning the full length cDNA (NM\_018407, ID=55353, Figure 1) harboring this fragment was performed by Expressed Sequence Tag (EST) splicing, 5' rapid amplification

**1. Introduction** 

their specificity or sensitivity.
