Expression of deleted in malignant brain tumours 1 (DMBT1) relates to the proliferation and malignant transformation of hepatic progenitor cells in hepatitis B virus-related liver diseases.
OBJECTIVE
The molecular mechanisms underlying proliferation and malignant transformation of hepatic progenitor cells (HPCs) remain largely unknown. The purpose of this study was to evaluate the correlation between the expression of deleted in malignant brain tumours 1 (DMBT1) and the biological behaviour of HPCs in different hepatitis B virus (HBV)-related human liver diseases.


RESULTS
Expression of DMBT1 in HPCs was investigated by double immunofluorescence labelling in control-group and HBV-related liver diseases, including hepatitis, hepatocellular carcinoma (HCC), non-tumoral liver tissue away from HCC, non-tumoral cirrhotic tissue adjacent to HCC, and non-HCC cirrhosis. DMBT1-positive HPCs were isolated by laser capture microdissection and subjected to duplex polymerase chain reaction in order to detect homozygous deletion of DMBT1. The number of DMBT1-positive HPCs increased in direct proportion to inflammation severity. Loss of heterozygosity for DMBT1 was more frequent in HCC tumour area and non-tumoral cirrhotic tissue adjacent to HCC, compared with other HBV-related liver diseases (P < 0.05).


CONCLUSIONS
DMBT1 may play an important role in the proliferation of HPCs in HBV-related liver diseases. Moreover, down-expression of DMBT1 might enhance the risk of malignant transformation of HPCs.
Department of Pathology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Huan
H
Deng
Ya-Bo
YB
Gao
Hua-Feng
HF
Wang
Xiao-Long
XL
Jin
Jia-Cheng
JC
Xiao
D000328:Adult; D000368:Aged; D001706:Biopsy; D002135:Calcium-Binding Proteins; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000821:virology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D004268:DNA-Binding Proteins; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006515:Hepatitis B virus; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D008107:Liver Diseases / Q000473:pathology* / Q000821:virology*; D008113:Liver Neoplasms / Q000473:pathology / Q000821:virology; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D013234:Stem Cells / Q000473:pathology*; D025521:Tumor Suppressor Proteins
D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins