Macrophage metalloelastase, a member of the human
matrix metalloproteinase family, is believed to play an important role in
angiostatin generation, which, in experimental studies, has an antiangiogenic function and is a key molecule in
tumor dormancy. However, no clinical studies have been reported regarding the correlation between
human macrophage metalloelastase (HME) gene expression and
angiostatin production. Therefore, the present study was designed to evaluate the HME
messenger RNA (
mRNA) expression and
angiostatin generation in
hepatocellular carcinoma (HCC). Tumorous and contiguous nontumorous tissues were obtained from 40 HCC patients who underwent curative partial
hepatectomy. By using Northern blot hybridization, HME
mRNA was detected in 25 of the 40 HCC samples and, in all of these cases, the expression in tumorous tissues was stronger than in the nontumorous tissues. In situ hybridization identified the HCC cells as mainly responsible for the signals shown in Northern blot.
Angiostatin was detected by Western blot mainly in
tumors and showed significant association with HME
mRNA expression in tumorous tissues (P = .0008). The patients whose
tumors did not express HME
mRNA and, thus, did not produce
angiostatin, demonstrated poorer survival than those whose
tumors showed high expression of HME
mRNA and
angiostatin generation (P = . 002). The univariate and multivariate analyses revealed that HME
mRNA expression is a new and independent variable affecting overall survival (P = .001 and P = .03, respectively). These findings show that the HME gene is expressed in HCC being significantly associated with
angiostatin generation by such
tumors and that HME
mRNA expression may serve as a new molecular prognostic marker in HCC patients after partial
hepatectomy.