Clinical impact of plasma TGF-beta1 and circulating TGF-beta1 mRNA in diagnosis of hepatocellular carcinoma.
BACKGROUND
Transforming growth factor-beta (TGF-beta) plays an important role in the regulation of cell growth and differentiation, angiogenesis, extracellular matrix formation, immunosuppression and cancer development. In this study, we investigated the levels of TGF-beta1 and TGF-beta1 mRNA expression, their relationship with HBV replication, and their diagnostic value for hepatocellular carcinoma (HCC).


METHODS
Total RNAs were extracted from HCC samples and matched non-tumor tissues, and from peripheral blood mononuclear cells in HCC patients. TGF-beta1 mRNA was amplified by RT-PCR and confirmed by DNA sequencing. The distribution of TGF-beta1 expression was assessed by immunohistochemistry. The clinical characteristics were analyzed between TGF-beta1 and HBV replication. The diagnostic value of circulating TGF-beta1 and TGF-beta1 mRNA levels were investigated in HCC patients.


RESULTS
The incidence of hepatic TGF-beta1 expression was 83.3% in HCC samples, 43.3% in the surrounding tissues, 94.7% in the HBV DNA-positive group, and 63.6% in the HBV DNA-negative group. Liver TGF-beta1 expression was associated with the degree of HCC differentiation and the status of HBV replication, but not with the size or number of tumors. Circulating TGF-beta1 level and incidence of TGF-beta1 mRNA were significantly higher in the HCC group than in any group of patients with benign liver disease, with a higher sensitivity of 89.5% and a specificity of 94.0% for HCC diagnosis when circulating TGF-beta1 levels were >1.2 microg/L. No significant correlation was found between TGF-beta1 expression and AFP level or tumor size. Combining TGF-beta1 level and serum AFP raised the detection rate to 97.4%.


CONCLUSIONS
Abnormal expression of hepatic TGF-beta1 is associated with the degree of HCC differentiation and HBV replication. Both circulating TGF-beta1 and TGF-beta1 mRNA can be used as sensitive biomarkers for the diagnosis and prognosis of HBV-induced HCC.
Dong
Zhi-Zhen
ZZ
Department of Diagnostics, Affiliated Hospital, Nantong University, Nantong 226001, China.
Yao
Deng-Fu
DF
Yao
Min
M
Qiu
Li-Wei
LW
Zong
Lei
L
Wu
Wei
W
Wu
Xin-Hua
XH
Yao
Deng-Bing
DB
Meng
Xian-Yong
XY
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000175:diagnosis / Q000821:virology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000150:complications / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000097:blood* / Q000235:genetics*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1