RESUMEN
BACKGROUND/AIMS: The molecules involved in the progression of hepatocellular carcinoma (HCC) are not fully understood. The aim of this study was to elucidate the crucial genes involved in cancer progression and metastasis. METHODS: Selectively expressed genes were screened using differential display analysis, and then further analyzed by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: Tetraspanin CO-029 was found to be frequently and significantly overexpressed in HCC. Real-time quantitative RT-PCR showed that the CO-029 mRNA level was 1.7 times higher (P=0.030) in cancerous tissues than in non-cancerous tissues. mRNA expression of the other tetraspanins, CD9 and CD82, was downregulated in HCC, especially in tumors with intrahepatic spreading (portal vein invasion and/or intrahepatic metastasis). In contrast, mRNA expression of CO-029 tended to be increased in cancerous tissue showing intrahepatic spreading compared with tumors without such spreading. Immunohistochemical analysis revealed that CO-029 was overexpressed in poorly differentiated HCCs compared with well to moderately differentiated tumors (P<0.001), and in HCCs showing intrahepatic spreading compared with those without spreading (P=0.019). CONCLUSIONS: Our findings suggest that CO-029 has some roles in the promotion of metastasis of HCC.
Asunto(s)
Antígenos de Neoplasias/genética , Carcinoma Hepatocelular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , Glicoproteínas de Membrana/genética , Proteínas de la Membrana/genética , Transcripción Genética , Adulto , Anciano , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Cartilla de ADN , Femenino , Perfilación de la Expresión Génica , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Masculino , Proteínas de la Membrana/análisis , Persona de Mediana Edad , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , TetraspaninasRESUMEN
Few genes related to carcinogenesis and progression of hepatocellular carcinoma (HCC) have been identified to date. In the present study, we report the cloning and characterization of a novel gene, DRH1, which is frequently down-regulated in HCC. The full-length DRH1 clone contains an open reading frame of 1257 nucleotides encoding 419 amino acids. The deduced DRH1 protein shows 41% identity to VDUP1, expression of which is rapidly induced by 1,25-dihydroxyvitamin D3. The DRH1 gene was localized to chromosome 15, and DRH1 protein was mainly observed in the cytoplasm of transiently transfected cells. Real-time quantitative reverse transcription-PCR analysis showed that the expression level of DRH1 was reduced in 29 of 35 (83%) HCCs compared with corresponding noncancerous liver tissue. The average (mean +/- SE) ratio of DRH1 expression level in tumor to corresponding noncancerous tissue was significantly different between well, moderately, and poorly differentiated HCCs (1.15 +/- 0.23, 0.69 +/- 0.10, and 0.19 +/- 0.04, respectively) and between HCCs without and with vascular invasion (0.94 +/- 0.16 and 0.46 +/- 0.07, respectively). These results indicate that the down-regulation of DRH1 occurs not at an early stage but rather at a late stage of HCC progression. Although the function of DRH1 protein is still unknown, our findings suggest that DRH1 is related to the progression of HCC and may provide a new prognostic factor.