Expression of heat shock proteins (HSP27, HSP60, HSP70, HSP90, GRP78, GRP94) in hepatitis B virus-related hepatocellular carcinomas and dysplastic nodules.
OBJECTIVE
Expression of heat shock proteins (HSPs) is frequently up-regulated in hepatocellular carcinoma (HCC), which evolves from dysplastic nodule (DN) and early HCC to advanced HCC. However, little is known about the differential expression of HSPs in multistep hepatocarcinogenesis. It was the purpose of this study to monitor the expression of HSPs in multistep hepatocarcinogenesis and to evaluate their prognostic significance in hepatitis B virus (HBV)-related HCC.


METHODS
Thirty-eight HCC and 19 DN samples were obtained from 52 hepatitis B surface antigen-positive Korean patients. Immunohistochemical and dot immunoblot analyses of HSP27, HSP60, HSP70, HSP90, glucose regulated protein (GRP)78, and GRP94 were performed and their expression at different stages of HCC development was statistically analyzed.


RESULTS
Expression of HSP27, HSP70, HSP90, GRP78, and GRP94 increased along with the stepwise progression of hepatocarcinogenesis. Strong correlation was found only in GRP78 (Spearman's r = 0.802). There was a positive correlation between the expressions of GRP78, GRP94, HSP90, or HSP70 and prognostic factors of HCC. Specifically, the expression of GRP78, GRP94, or HSP90 was associated significantly with vascular invasion and intrahepatic metastasis.


CONCLUSIONS
The expressions of HSPs are commonly up-regulated in HBV-related HCCs and GRP78 might play an important role in the stepwise progression of HBV-related hepatocarcinogenesis. GRP78, GRP94, and HSP90 may be important prognostic markers of HBV-related HCC, strongly suggesting vascular invasion and intrahepatic metastasis.
Lim
Seung-Oe
SO
School of Biological Sciences, Seoul National University, Seoul, Korea.
Park
Sung-Gyoo
SG
Yoo
Jun-Hi
JH
Park
Young-Min
YM
Kim
Hie-Joon
HJ
Jang
Kee-Taek
KT
Cho
Jae-Won
JW
Yoo
Byung-Chul
BC
Jung
Gu-Hung
GH
Park
Cheol-Keun
CK
D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology; D018834:Chaperonin 60 / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000378:metabolism* / Q000821:virology; D008565:Membrane Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D018834:Chaperonin 60; D000091342:Endoplasmic Reticulum Chaperone BiP; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C000717247:HSPA5 protein, human; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; C018551:glucose-regulated proteins