The gene expression level of transforming growth factor-beta (TGF-beta) as a biological prognostic marker of hepatocellular carcinoma.
The question that transforming growth factor-beta (TGF-beta) provides a tumor-suppressive or a tumor promoting role is still unknown in hepatocellular carcinoma (HCC). In the present study, we quantitatively investigated the gene expression levels of TGF-beta in liver tissues from patients with HCC. We also evaluated the prognostic importance of TGF-beta gene in HCC patients. A total of 59 patients with primary HCC who underwent hepatectomy between 1993 and 2001 were enrolled. TGF-beta gene expression levels of tumors and of noncancerous livers were analyzed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The percentage of apoptotic cells in tumor cells (apoptotic index: AI) was evaluated with immunohistochemistry. Also the expression of survivin protein (apoptosis inhibitor) in tumors was detected by immunohistochemistry. TGF-beta gene expression levels of tumors were compared with clinicopathological findings of patients. The relative expression level of TGF-beta mRNA of 59 tumor tissues did not differ from those of 8 normal liver tissues or 59 noncancerous liver tissues. The mean AI of 29 tumors with normal expression levels of TGF-beta gene (4%) was significantly higher than that of 30 tumors with low expression levels of TGF-beta gene (2.5%, p = 0.03). Thirteen out of 30 tumors (43%) with low expression level of TGF-P gene showed survivin positive, while only 4 out of 29 tumors (14%) with preserved expression of TGF-beta gene showed survivin positive. This difference was significant (p = 0.012). The overall 5-year survival rate of 29 patients with tumors with preserved TGF-beta gene prolonged to 72% compared with that of 30 patients who had tumors with suppressed TGF-beta gene (58%, p = 0.156). In HCC, TGF-beta gene may play a defensive role against tumor progression by regulating survivin protein expression and by controlling occurrence of spontaneous apoptosis in tumors.
Ikeguchi
M
M
Div. of Operating Room, Faculty of Medicine, Tottori University, Yonago, Japan. masaike@grape.med.tottori-u.ac.jp
Iwamoto
A
A
Taniguchi
K
K
Katano
K
K
Hirooka
Y
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D015291:Transforming Growth Factors / Q000235:genetics*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D015291:Transforming Growth Factors