TY - JOUR
T1 - Reduced transforming growth factor-β receptor II expression in hepatocellular carcinoma correlates with intrahepatic metastasis
AU - Mamiya, Takao
AU - Yamazaki, Ken
AU - Masugi, Yohei
AU - Mori, Taisuke
AU - Effendi, Kathryn
AU - Du, Wenlin
AU - Hibi, Taizo
AU - Tanabe, Minoru
AU - Ueda, Masakazu
AU - Takayama, Tadatoshi
AU - Sakamoto, Michiie
N1 - Funding Information:
This study was supported by Grant-in-aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT); grants for the Health and Labor Sciences Research and the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor, and Welfare of Japan; and Research Grants for Life Sciences and Medicine from the Keio University Medical Science Fund.
PY - 2010/9
Y1 - 2010/9
N2 - Hepatocellular carcinoma (HCC) occurs mainly in the liver associated with chronic hepatitis and hepatic cirrhosis as a result of prolonged viral infection. Transforming growth factor-Β (TGF-Β) induces the fibrosis in hepatic cirrhosis, although it is also an inhibitor of hepatocyte proliferation. To understand the role of TGF-Β signaling in HCC progression, we analyzed gene expression in HCC cells in relation to TGF-Β signaling using a two-way clustering algorithm. By the analysis, five HCC cell lines were classified into two groups according to their metastatic capacity. TGF-Β receptor II (TGFBR2) was downregulated in metastatic cells, which did not show a response to TGF-Β. Immunohistochemistry demonstrated clear membrane distribution of TGFBR2 in noncancerous hepatocytes, whereas reduced TGFBR2 expression was observed in 34 of 136 HCCs. In clinical cases, reduced TGFBR2 expression correlated with larger tumor size (P0.001), poor differentiation (P0.001), portal vein invasion (P0.002), intrahepatic metastasis (IM) (P0.001), and shorter recurrence-free survival (P0.022). In conclusion, reduced TGFBR2 expression was associated with aggressive features of HCC such as IM, and may represent an immunohistochemical biomarker to detect aggressive HCC.
AB - Hepatocellular carcinoma (HCC) occurs mainly in the liver associated with chronic hepatitis and hepatic cirrhosis as a result of prolonged viral infection. Transforming growth factor-Β (TGF-Β) induces the fibrosis in hepatic cirrhosis, although it is also an inhibitor of hepatocyte proliferation. To understand the role of TGF-Β signaling in HCC progression, we analyzed gene expression in HCC cells in relation to TGF-Β signaling using a two-way clustering algorithm. By the analysis, five HCC cell lines were classified into two groups according to their metastatic capacity. TGF-Β receptor II (TGFBR2) was downregulated in metastatic cells, which did not show a response to TGF-Β. Immunohistochemistry demonstrated clear membrane distribution of TGFBR2 in noncancerous hepatocytes, whereas reduced TGFBR2 expression was observed in 34 of 136 HCCs. In clinical cases, reduced TGFBR2 expression correlated with larger tumor size (P0.001), poor differentiation (P0.001), portal vein invasion (P0.002), intrahepatic metastasis (IM) (P0.001), and shorter recurrence-free survival (P0.022). In conclusion, reduced TGFBR2 expression was associated with aggressive features of HCC such as IM, and may represent an immunohistochemical biomarker to detect aggressive HCC.
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U2 - 10.1038/labinvest.2010.105
DO - 10.1038/labinvest.2010.105
M3 - Article
C2 - 20531292
AN - SCOPUS:77956100350
SN - 0023-6837
VL - 90
SP - 1339
EP - 1345
JO - Laboratory investigation; a journal of technical methods and pathology
JF - Laboratory investigation; a journal of technical methods and pathology
IS - 9
ER -
