RESUMO
Hepatocellular carcinoma (HCC) is a common malignant solid tumor characterized by rich vascularization. Pregnancy-specific glycoprotein 9 (PSG9) is a member of the carcinoembryonic antigen (CEA)/PSG family and is produced at high levels during pregnancy. We previously identified PSG9 as an HCC-related protein. However, the expression of PSG9 and its regulation during HCC carcinogenesis remain poorly explored. In the present study, we first found that the levels of PSG9 protein were significantly increased in the plasma of HCC patients. PSG9 overexpression also increased the proliferation ability of an HCC cell line. High expression of PSG9 was associated with angiogenesis by accelerating VEGFA expression. In addition, Cox's proportional hazards model analysis revealed that the plasma level of PSG9 was an independent prognostic factor for overall survival. We propose that PSG9 is a novel indicator of prognosis in patients with HCC and could serve as a novel therapeutic target for HCC. Furthermore, our results indicate that PSG9 protein may facilitate the development of HCC by fostering angiogenesis via promoting VEGFA production in cancer cells.
Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Neovascularização Patológica/metabolismo , Glicoproteínas beta 1 Específicas da Gravidez/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/sangue , Neovascularização Patológica/genética , Glicoproteínas beta 1 Específicas da Gravidez/classificação , Glicoproteínas beta 1 Específicas da Gravidez/genética , Prognóstico , Interferência de RNA , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Pregnancy-specific beta 1-glycoproteins (PSGs) represent a large group (approximately 12-15) of proteins, related to members of the carcinoembryonic antigen family, that are abundant in placental tissue and in the sera of pregnant women. We describe the isolation and characterization of two additional PSG cDNAs, PSG9 and PSG10, whose transcripts are largely expressed in placental tissue and to a lesser extent in some other cell types, including myeloid cells differentiated to granulocytes. PSG9 and PSG10 are representatives of two distinct classes of PSG protein that have N-termini with or without the Arg-Gly-Asp motif implicated in adhesion. In addition to this distinction at the amino acid level, our analysis of several PSG cDNAs suggests that the transcription units encoding these proteins may be further distinguished in their 3' untranslated sequences, thus suggesting possibilities for transcriptional regulation of the two major protein classes.
