Decreased BMP-7 and p-Smad1/5/8 expression, and increased levels of gremlin in hepatocellular carcinoma.

Abstract

The aim of the present study was to investigate the expression of bone morphogenetic protein-7 (BMP-7), gremlin, and p-Smad/1/5/8 in carcinomatous and para-carcinoma tissue specimens from patients with hepatocellular carcinoma (HCC). The association of serum BMP-7 levels with clinicopathological parameters was examined to assess its relevance as a clinical biomarker for HCC. A total of 27 patients with HCC and 7 healthy subjects were included. Gene expression levels of BMP-7 and p-Smad1/5/8 were examined by reverse transcription-quantitative polymerase chain reaction. Immunohistochemical and western blot analysis were performed to determine the protein expression of target genes. The serum levels of BMP-7 were assessed by enzyme linked immunosorbent assay. The mRNA and protein expression of BMP-7 and gremlin were significantly down- and upregulated in HCC tumor tissues, respectively, compared with para-carcinoma tissues (P<0.05). The association of BMP-7 and gremlin expression with the differentiation status of HCC was also analyzed. There was a relatively higher level of BMP-7 and a lower level of gremlin expression in tumor tissues from patients with highly differentiated HCC when compared with poorly or moderately differentiated HCC (BMP-7, F=42.29, P<0.01; gremlin, F=37.93, P<0.01). Furthermore, the level of BMP-7 and p-Smad1/5/8 was decreased in patients with advanced stages of HCC, when compared with stage I HCC. The findings from the present study suggest that the BMP-7/p-Smad signaling pathway may be involved in the pathogenesis of HCC. The serum levels of BMP-7 may serve as a potential biomarker for HCC.