Evaluation of serum matrix metalloproteinase (MMP)-9 to MMP-2 ratio as a biomarker in hepatocellular carcinoma.
OBJECTIVE
Serum matrix metalloproteinase (MMP)-9/ MMP-2 ratios are highly associated with alpha-fetoprotein levels in patients with chronic hepatitis B. In this study, we evaluate the clinical usefulness of this ratio as a biomarker in hepatitis B virus-related hepatocellular carcinoma (HCC).


METHODS
Serum samples from 181 chronic hepatitis B patients (52 healthy carriers, 47 chronic hepatitis patients, 50 cirrhosis patients, and 32 HCC patients) were collected. MMP-9/ MMP-2 ratio was determined by zymography. The results were analyzed using the Receiver-Operating Characteristic (ROC) curve.


RESULTS
Serum MMP-9/ MMP-2 ratios in HCC patients were significantly higher than those in healthy carriers, chronic hepatitis patients, and cirrhosis patients (p = 0.004, 0.034, and < 0.001, respectively). The sensitivity and specificity at the optimal cutoff (0.97) were 69.7% and 73.4%, respectively. Significantly higher MMP-9/ MMP-2 ratios were found in advanced, inoperable HCC patients, compared to those in early stage HCC patients (p = 0.005). No significant difference was found for alpha-fetoprotein levels between these two groups (p = 0.312).


CONCLUSIONS
The serum MMP-9/ MMP-2 ratio can be used as an accessory diagnostic marker in hepatitis B virus-related HCC. This ratio is useful in distinguishing between patients with early stage HCC and those with advanced HCC.
Yeh
Huei-Chung
HC
Liver Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan.
Lin
Shi-Ming
SM
Chen
Miin-Fu
MF
Pan
Tai-Long
TL
Wang
Pei-Wen
PW
Yeh
Chau-Ting
CT
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000201:enzymology* / Q000821:virology; D002353:Carrier State / Q000201:enzymology / Q000473:pathology / Q000821:virology; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D019694:Hepatitis B, Chronic / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008103:Liver Cirrhosis / Q000201:enzymology* / Q000473:pathology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000201:enzymology* / Q000821:virology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D011237:Predictive Value of Tests
D015415:Biomarkers; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9