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.
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